The type species of ORTHOPOXVIRUS, related to COWPOX VIRUS, but whose true origin is unknown. It has been used as a live vaccine against SMALLPOX. It is also used as a vector for inserting foreign DNA into animals. Rabbitpox virus is a subspecies of VACCINIA VIRUS.
The cutaneous and occasional systemic reactions associated with vaccination using smallpox (variola) vaccine.
The process of intracellular viral multiplication, consisting of the synthesis of PROTEINS; NUCLEIC ACIDS; and sometimes LIPIDS, and their assembly into a new infectious particle.
Proteins found in any species of virus.
Established cell cultures that have the potential to propagate indefinitely.
Deoxyribonucleic acid that makes up the genetic material of viruses.
Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.
Ribonucleic acid that makes up the genetic material of viruses.
The functional hereditary units of VIRUSES.
A family of double-stranded DNA viruses infecting mammals (including humans), birds and insects. There are two subfamilies: CHORDOPOXVIRINAE, poxviruses of vertebrates, and ENTOMOPOXVIRINAE, poxviruses of insects.
Any of the processes by which cytoplasmic factors influence the differential control of gene action in viruses.
Viruses whose genetic material is RNA.
The first continuously cultured human malignant CELL LINE, derived from the cervical carcinoma of Henrietta Lacks. These cells are used for VIRUS CULTIVATION and antitumor drug screening assays.
The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.
The assembly of VIRAL STRUCTURAL PROTEINS and nucleic acid (VIRAL DNA or VIRAL RNA) to form a VIRUS PARTICLE.
Method for measuring viral infectivity and multiplication in CULTURED CELLS. Clear lysed areas or plaques develop as the VIRAL PARTICLES are released from the infected cells during incubation. With some VIRUSES, the cells are killed by a cytopathic effect; with others, the infected cells are not killed but can be detected by their hemadsorptive ability. Sometimes the plaque cells contain VIRAL ANTIGENS which can be measured by IMMUNOFLUORESCENCE.
A species of ORTHOPOXVIRUS that is the etiologic agent of COWPOX. It is closely related to but antigenically different from VACCINIA VIRUS.
A species of ORTHOPOXVIRUS causing infections in humans. No infections have been reported since 1977 and the virus is now believed to be virtually extinct.
The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.
The type species of LENTIVIRUS and the etiologic agent of AIDS. It is characterized by its cytopathic effect and affinity for the T4-lymphocyte.
An acute, highly contagious, often fatal infectious disease caused by an orthopoxvirus characterized by a biphasic febrile course and distinctive progressive skin eruptions. Vaccination has succeeded in eradicating smallpox worldwide. (Dorland, 28th ed)
A CELL LINE derived from the kidney of the African green (vervet) monkey, (CERCOPITHECUS AETHIOPS) used primarily in virus replication studies and plaque assays.
A species of CERCOPITHECUS containing three subspecies: C. tantalus, C. pygerythrus, and C. sabeus. They are found in the forests and savannah of Africa. The African green monkey (C. pygerythrus) is the natural host of SIMIAN IMMUNODEFICIENCY VIRUS and is used in AIDS research.
Agents used in the prophylaxis or therapy of VIRUS DISEASES. Some of the ways they may act include preventing viral replication by inhibiting viral DNA polymerase; binding to specific cell-surface receptors and inhibiting viral penetration or uncoating; inhibiting viral protein synthesis; or blocking late stages of virus assembly.
The infective system of a virus, composed of the viral genome, a protein core, and a protein coat called a capsid, which may be naked or enclosed in a lipoprotein envelope called the peplos.
Process of growing viruses in live animals, plants, or cultured cells.
DNA molecules capable of autonomous replication within a host cell and into which other DNA sequences can be inserted and thus amplified. Many are derived from PLASMIDS; BACTERIOPHAGES; or VIRUSES. They are used for transporting foreign genes into recipient cells. Genetic vectors possess a functional replicator site and contain GENETIC MARKERS to facilitate their selective recognition.
Substances elaborated by viruses that have antigenic activity.
Production of new arrangements of DNA by various mechanisms such as assortment and segregation, CROSSING OVER; GENE CONVERSION; GENETIC TRANSFORMATION; GENETIC CONJUGATION; GENETIC TRANSDUCTION; or mixed infection of viruses.
Specific molecular components of the cell capable of recognizing and interacting with a virus, and which, after binding it, are capable of generating some signal that initiates the chain of events leading to the biological response.
Virus diseases caused by the POXVIRIDAE.
A live VACCINIA VIRUS vaccine of calf lymph or chick embryo origin, used for immunization against smallpox. It is now recommended only for laboratory workers exposed to smallpox virus. Certain countries continue to vaccinate those in the military service. Complications that result from smallpox vaccination include vaccinia, secondary bacterial infections, and encephalomyelitis. (Dorland, 28th ed)
Extrachromosomal, usually CIRCULAR DNA molecules that are self-replicating and transferable from one organism to another. They are found in a variety of bacterial, archaeal, fungal, algal, and plant species. They are used in GENETIC ENGINEERING as CLONING VECTORS.
Viruses which lack a complete genome so that they cannot completely replicate or cannot form a protein coat. Some are host-dependent defectives, meaning they can replicate only in cell systems which provide the particular genetic function which they lack. Others, called SATELLITE VIRUSES, are able to replicate only when their genetic defect is complemented by a helper virus.
Small synthetic peptides that mimic surface antigens of pathogens and are immunogenic, or vaccines manufactured with the aid of recombinant DNA techniques. The latter vaccines may also be whole viruses whose nucleic acids have been modified.
Immunoglobulins produced in response to VIRAL ANTIGENS.
The biosynthesis of RNA carried out on a template of DNA. The biosynthesis of DNA from an RNA template is called REVERSE TRANSCRIPTION.
Species of the genus LENTIVIRUS, subgenus primate immunodeficiency viruses (IMMUNODEFICIENCY VIRUSES, PRIMATE), that induces acquired immunodeficiency syndrome in monkeys and apes (SAIDS). The genetic organization of SIV is virtually identical to HIV.
A general term for diseases produced by viruses.
Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.
The type species of ALPHAVIRUS normally transmitted to birds by CULEX mosquitoes in Egypt, South Africa, India, Malaya, the Philippines, and Australia. It may be associated with fever in humans. Serotypes (differing by less than 17% in nucleotide sequence) include Babanki, Kyzylagach, and Ockelbo viruses.
Viral proteins that are components of the mature assembled VIRUS PARTICLES. They may include nucleocapsid core proteins (gag proteins), enzymes packaged within the virus particle (pol proteins), and membrane components (env proteins). These do not include the proteins encoded in the VIRAL GENOME that are produced in infected cells but which are not packaged in the mature virus particle,i.e. the so called non-structural proteins (VIRAL NONSTRUCTURAL PROTEINS).
The expelling of virus particles from the body. Important routes include the respiratory tract, genital tract, and intestinal tract. Virus shedding is an important means of vertical transmission (INFECTIOUS DISEASE TRANSMISSION, VERTICAL).
Layers of protein which surround the capsid in animal viruses with tubular nucleocapsids. The envelope consists of an inner layer of lipids and virus specified proteins also called membrane or matrix proteins. The outer layer consists of one or more types of morphological subunits called peplomers which project from the viral envelope; this layer always consists of glycoproteins.
A genus of the family POXVIRIDAE, subfamily CHORDOPOXVIRINAE, comprising many species infecting mammals. Viruses of this genus cause generalized infections and a rash in some hosts. The type species is VACCINIA VIRUS.
The type species of the genus AVIPOXVIRUS. It is the etiologic agent of FOWLPOX.
The complete genetic complement contained in a DNA or RNA molecule in a virus.
Tumor-selective, replication competent VIRUSES that have antineoplastic effects. This is achieved by producing cytotoxicity-enhancing proteins and/or eliciting an antitumor immune response. They are genetically engineered so that they can replicate in CANCER cells but not in normal cells, and are used in ONCOLYTIC VIROTHERAPY.
Visible morphologic changes in cells infected with viruses. It includes shutdown of cellular RNA and protein synthesis, cell fusion, release of lysosomal enzymes, changes in cell membrane permeability, diffuse changes in intracellular structures, presence of viral inclusion bodies, and chromosomal aberrations. It excludes malignant transformation, which is CELL TRANSFORMATION, VIRAL. Viral cytopathogenic effects provide a valuable method for identifying and classifying the infecting viruses.
The measurement of infection-blocking titer of ANTISERA by testing a series of dilutions for a given virus-antiserum interaction end-point, which is generally the dilution at which tissue cultures inoculated with the serum-virus mixtures demonstrate cytopathology (CPE) or the dilution at which 50% of test animals injected with serum-virus mixtures show infectivity (ID50) or die (LD50).
Viruses whose nucleic acid is DNA.
Suspensions of attenuated or killed viruses administered for the prevention or treatment of infectious viral disease.
Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.
Proteins found mainly in icosahedral DNA and RNA viruses. They consist of proteins directly associated with the nucleic acid inside the NUCLEOCAPSID.
The type species of the genus ORTHOHEPADNAVIRUS which causes human HEPATITIS B and is also apparently a causal agent in human HEPATOCELLULAR CARCINOMA. The Dane particle is an intact hepatitis virion, named after its discoverer. Non-infectious spherical and tubular particles are also seen in the serum.
The type species of MORBILLIVIRUS and the cause of the highly infectious human disease MEASLES, which affects mostly children.
The interactions between a host and a pathogen, usually resulting in disease.
A group of viruses in the PNEUMOVIRUS genus causing respiratory infections in various mammals. Humans and cattle are most affected but infections in goats and sheep have also been reported.
A species of POLYOMAVIRUS originally isolated from Rhesus monkey kidney tissue. It produces malignancy in human and newborn hamster kidney cell cultures.
Proteins which bind to DNA. The family includes proteins which bind to both double- and single-stranded DNA and also includes specific DNA binding proteins in serum which can be used as markers for malignant diseases.
Viruses parasitic on plants higher than bacteria.
Proteins prepared by recombinant DNA technology.
Proteins encoded by a VIRAL GENOME that are produced in the organisms they infect, but not packaged into the VIRUS PARTICLES. Some of these proteins may play roles within the infected cell during VIRUS REPLICATION or act in regulation of virus replication or VIRUS ASSEMBLY.
The mechanism by which latent viruses, such as genetically transmitted tumor viruses (PROVIRUSES) or PROPHAGES of lysogenic bacteria, are induced to replicate and then released as infectious viruses. It may be effected by various endogenous and exogenous stimuli, including B-cell LIPOPOLYSACCHARIDES, glucocorticoid hormones, halogenated pyrimidines, IONIZING RADIATION, ultraviolet light, and superinfecting viruses.
A single-stranded DNA-binding protein that is found in EUKARYOTIC CELLS. It is required for DNA REPLICATION; DNA REPAIR; and GENETIC RECOMBINATION.
The type species of VESICULOVIRUS causing a disease symptomatically similar to FOOT-AND-MOUTH DISEASE in cattle, horses, and pigs. It may be transmitted to other species including humans, where it causes influenza-like symptoms.
The ability of a pathogenic virus to lie dormant within a cell (latent infection). In eukaryotes, subsequent activation and viral replication is thought to be caused by extracellular stimulation of cellular transcription factors. Latency in bacteriophage is maintained by the expression of virally encoded repressors.
A subfamily in the family MURIDAE, comprising the hamsters. Four of the more common genera are Cricetus, CRICETULUS; MESOCRICETUS; and PHODOPUS.
Use of attenuated VIRUSES as ANTINEOPLASTIC AGENTS to selectively kill CANCER cells.
A subtype of INFLUENZA A VIRUS with the surface proteins hemagglutinin 1 and neuraminidase 1. The H1N1 subtype was responsible for the Spanish flu pandemic of 1918.
The type species of SIMPLEXVIRUS causing most forms of non-genital herpes simplex in humans. Primary infection occurs mainly in infants and young children and then the virus becomes latent in the dorsal root ganglion. It then is periodically reactivated throughout life causing mostly benign conditions.
The type species of LYSSAVIRUS causing rabies in humans and other animals. Transmission is mostly by animal bites through saliva. The virus is neurotropic multiplying in neurons and myotubes of vertebrates.
Includes the spectrum of human immunodeficiency virus infections that range from asymptomatic seropositivity, thru AIDS-related complex (ARC), to acquired immunodeficiency syndrome (AIDS).
The quantity of measurable virus in a body fluid. Change in viral load, measured in plasma, is sometimes used as a SURROGATE MARKER in disease progression.
The degree of pathogenicity within a group or species of microorganisms or viruses as indicated by case fatality rates and/or the ability of the organism to invade the tissues of the host. The pathogenic capacity of an organism is determined by its VIRULENCE FACTORS.
A subtype of INFLUENZA A VIRUS comprised of the surface proteins hemagglutinin 5 and neuraminidase 1. The H5N1 subtype, frequently referred to as the bird flu virus, is endemic in wild birds and very contagious among both domestic (POULTRY) and wild birds. It does not usually infect humans, but some cases have been reported.
A critical subpopulation of regulatory T-lymphocytes involved in MHC Class I-restricted interactions. They include both cytotoxic T-lymphocytes (T-LYMPHOCYTES, CYTOTOXIC) and CD8+ suppressor T-lymphocytes.
A species of ORTHOPOXVIRUS causing an epidemic disease among captive primates.
The uptake of naked or purified DNA by CELLS, usually meaning the process as it occurs in eukaryotic cells. It is analogous to bacterial transformation (TRANSFORMATION, BACTERIAL) and both are routinely employed in GENE TRANSFER TECHNIQUES.
Short sequences (generally about 10 base pairs) of DNA that are complementary to sequences of messenger RNA and allow reverse transcriptases to start copying the adjacent sequences of mRNA. Primers are used extensively in genetic and molecular biology techniques.
Any DNA sequence capable of independent replication or a molecule that possesses a REPLICATION ORIGIN and which is therefore potentially capable of being replicated in a suitable cell. (Singleton & Sainsbury, Dictionary of Microbiology and Molecular Biology, 2d ed)
A species of FLAVIVIRUS, one of the Japanese encephalitis virus group (ENCEPHALITIS VIRUSES, JAPANESE). It can infect birds and mammals. In humans, it is seen most frequently in Africa, Asia, and Europe presenting as a silent infection or undifferentiated fever (WEST NILE FEVER). The virus appeared in North America for the first time in 1999. It is transmitted mainly by CULEX spp mosquitoes which feed primarily on birds, but it can also be carried by the Asian Tiger mosquito, AEDES albopictus, which feeds mainly on mammals.
The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments.
A sequence of successive nucleotide triplets that are read as CODONS specifying AMINO ACIDS and begin with an INITIATOR CODON and end with a stop codon (CODON, TERMINATOR).
The outer protein protective shell of a virus, which protects the viral nucleic acid.
The type species of LEPORIPOXVIRUS causing infectious myxomatosis, a severe generalized disease, in rabbits. Tumors are not always present.
An enzyme that catalyses RNA-template-directed extension of the 3'- end of an RNA strand by one nucleotide at a time, and can initiate a chain de novo. (Enzyme Nomenclature, 1992, p293)
A critical subpopulation of T-lymphocytes involved in the induction of most immunological functions. The HIV virus has selective tropism for the T4 cell which expresses the CD4 phenotypic marker, a receptor for HIV. In fact, the key element in the profound immunosuppression seen in HIV infection is the depletion of this subset of T-lymphocytes.
A genus of FLAVIVIRIDAE causing parenterally-transmitted HEPATITIS C which is associated with transfusions and drug abuse. Hepatitis C virus is the type species.
A suborder of PRIMATES consisting of six families: CEBIDAE (some New World monkeys), ATELIDAE (some New World monkeys), CERCOPITHECIDAE (Old World monkeys), HYLOBATIDAE (gibbons and siamangs), CALLITRICHINAE (marmosets and tamarins), and HOMINIDAE (humans and great apes).
A genus of the family HERPESVIRIDAE, subfamily BETAHERPESVIRINAE, infecting the salivary glands, liver, spleen, lungs, eyes, and other organs, in which they produce characteristically enlarged cells with intranuclear inclusions. Infection with Cytomegalovirus is also seen as an opportunistic infection in AIDS.
A genus of the family HERPESVIRIDAE, subfamily ALPHAHERPESVIRINAE, consisting of herpes simplex-like viruses. The type species is HERPESVIRUS 1, HUMAN.
Immunized T-lymphocytes which can directly destroy appropriate target cells. These cytotoxic lymphocytes may be generated in vitro in mixed lymphocyte cultures (MLC), in vivo during a graft-versus-host (GVH) reaction, or after immunization with an allograft, tumor cell or virally transformed or chemically modified target cell. The lytic phenomenon is sometimes referred to as cell-mediated lympholysis (CML). These CD8-positive cells are distinct from NATURAL KILLER CELLS and NATURAL KILLER T-CELLS. There are two effector phenotypes: TC1 and TC2.
A cultured line of C3H mouse FIBROBLASTS that do not adhere to one another and do not express CADHERINS.
A genetic rearrangement through loss of segments of DNA or RNA, bringing sequences which are normally separated into close proximity. This deletion may be detected using cytogenetic techniques and can also be inferred from the phenotype, indicating a deletion at one specific locus.
Use of restriction endonucleases to analyze and generate a physical map of genomes, genes, or other segments of DNA.
RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.
A species of gram-negative, facultatively anaerobic, rod-shaped bacteria (GRAM-NEGATIVE FACULTATIVELY ANAEROBIC RODS) commonly found in the lower part of the intestine of warm-blooded animals. It is usually nonpathogenic, but some strains are known to produce DIARRHEA and pyogenic infections. Pathogenic strains (virotypes) are classified by their specific pathogenic mechanisms such as toxins (ENTEROTOXIGENIC ESCHERICHIA COLI), etc.
DNA-dependent DNA polymerases found in bacteria, animal and plant cells. During the replication process, these enzymes catalyze the addition of deoxyribonucleotide residues to the end of a DNA strand in the presence of DNA as template-primer. They also possess exonuclease activity and therefore function in DNA repair.
A subtype of INFLUENZA A VIRUS comprised of the surface proteins hemagglutinin 3 and neuraminidase 2. The H3N2 subtype was responsible for the Hong Kong flu pandemic of 1968.
Administration of vaccines to stimulate the host's immune response. This includes any preparation intended for active immunological prophylaxis.
The insertion of recombinant DNA molecules from prokaryotic and/or eukaryotic sources into a replicating vehicle, such as a plasmid or virus vector, and the introduction of the resultant hybrid molecules into recipient cells without altering the viability of those cells.
Acquired defect of cellular immunity that occurs naturally in macaques infected with SRV serotypes, experimentally in monkeys inoculated with SRV or MASON-PFIZER MONKEY VIRUS; (MPMV), or in monkeys infected with SIMIAN IMMUNODEFICIENCY VIRUS.
A mild, eruptive skin disease of milk cows caused by COWPOX VIRUS, with lesions occurring principally on the udder and teats. Human infection may occur while milking an infected animal.
Proteins that catalyze the unwinding of duplex DNA during replication by binding cooperatively to single-stranded regions of DNA or to short regions of duplex DNA that are undergoing transient opening. In addition DNA helicases are DNA-dependent ATPases that harness the free energy of ATP hydrolysis to translocate DNA strands.
The rate dynamics in chemical or physical systems.
Specific hemagglutinin subtypes encoded by VIRUSES.
The parts of a macromolecule that directly participate in its specific combination with another molecule.
Elements of limited time intervals, contributing to particular results or situations.
In vitro method for producing large amounts of specific DNA or RNA fragments of defined length and sequence from small amounts of short oligonucleotide flanking sequences (primers). The essential steps include thermal denaturation of the double-stranded target molecules, annealing of the primers to their complementary sequences, and extension of the annealed primers by enzymatic synthesis with DNA polymerase. The reaction is efficient, specific, and extremely sensitive. Uses for the reaction include disease diagnosis, detection of difficult-to-isolate pathogens, mutation analysis, genetic testing, DNA sequencing, and analyzing evolutionary relationships.
The presence of viruses in the blood.
Insertion of viral DNA into host-cell DNA. This includes integration of phage DNA into bacterial DNA; (LYSOGENY); to form a PROPHAGE or integration of retroviral DNA into cellular DNA to form a PROVIRUS.
Membrane glycoproteins from influenza viruses which are involved in hemagglutination, virus attachment, and envelope fusion. Fourteen distinct subtypes of HA glycoproteins and nine of NA glycoproteins have been identified from INFLUENZA A VIRUS; no subtypes have been identified for Influenza B or Influenza C viruses.
Proteins coded by the retroviral gag gene. The products are usually synthesized as protein precursors or POLYPROTEINS, which are then cleaved by viral proteases to yield the final products. Many of the final products are associated with the nucleoprotein core of the virion. gag is short for group-specific antigen.
The biosynthesis of PEPTIDES and PROTEINS on RIBOSOMES, directed by MESSENGER RNA, via TRANSFER RNA that is charged with standard proteinogenic AMINO ACIDS.
Biologically active DNA which has been formed by the in vitro joining of segments of DNA from different sources. It includes the recombination joint or edge of a heteroduplex region where two recombining DNA molecules are connected.
The temporal order in which the DNA of the GENOME is replicated.
An area showing altered staining behavior in the nucleus or cytoplasm of a virus-infected cell. Some inclusion bodies represent "virus factories" in which viral nucleic acid or protein is being synthesized; others are merely artifacts of fixation and staining. One example, Negri bodies, are found in the cytoplasm or processes of nerve cells in animals that have died from rabies.
Virus diseases caused by the ORTHOMYXOVIRIDAE.
A family of RNA viruses causing INFLUENZA and other diseases. There are five recognized genera: INFLUENZAVIRUS A; INFLUENZAVIRUS B; INFLUENZAVIRUS C; ISAVIRUS; and THOGOTOVIRUS.
Human immunodeficiency virus. A non-taxonomic and historical term referring to any of two species, specifically HIV-1 and/or HIV-2. Prior to 1986, this was called human T-lymphotropic virus type III/lymphadenopathy-associated virus (HTLV-III/LAV). From 1986-1990, it was an official species called HIV. Since 1991, HIV was no longer considered an official species name; the two species were designated HIV-1 and HIV-2.
The spatial arrangement of the atoms of a nucleic acid or polynucleotide that results in its characteristic 3-dimensional shape.
Vaccines or candidate vaccines containing inactivated HIV or some of its component antigens and designed to prevent or treat AIDS. Some vaccines containing antigens are recombinantly produced.
Live vaccines prepared from microorganisms which have undergone physical adaptation (e.g., by radiation or temperature conditioning) or serial passage in laboratory animal hosts or infected tissue/cell cultures, in order to produce avirulent mutant strains capable of inducing protective immunity.
Proteins that form the CAPSID of VIRUSES.
A species of ALPHAVIRUS isolated in central, eastern, and southern Africa.
The binding of virus particles to receptors on the host cell surface. For enveloped viruses, the virion ligand is usually a surface glycoprotein as is the cellular receptor. For non-enveloped viruses, the virus CAPSID serves as the ligand.
DNA sequences which are recognized (directly or indirectly) and bound by a DNA-dependent RNA polymerase during the initiation of transcription. Highly conserved sequences within the promoter include the Pribnow box in bacteria and the TATA BOX in eukaryotes.
Microscopy using an electron beam, instead of light, to visualize the sample, thereby allowing much greater magnification. The interactions of ELECTRONS with specimens are used to provide information about the fine structure of that specimen. In TRANSMISSION ELECTRON MICROSCOPY the reactions of the electrons that are transmitted through the specimen are imaged. In SCANNING ELECTRON MICROSCOPY an electron beam falls at a non-normal angle on the specimen and the image is derived from the reactions occurring above the plane of the specimen.
An enzyme that catalyzes the conversion of ATP and thymidine to ADP and thymidine 5'-phosphate. Deoxyuridine can also act as an acceptor and dGTP as a donor. (From Enzyme Nomenclature, 1992) EC
Deletion of sequences of nucleic acids from the genetic material of an individual.
The species Oryctolagus cuniculus, in the family Leporidae, order LAGOMORPHA. Rabbits are born in burrows, furless, and with eyes and ears closed. In contrast with HARES, rabbits have 22 chromosome pairs.
Any immunization following a primary immunization and involving exposure to the same or a closely related antigen.
Process of generating a genetic MUTATION. It may occur spontaneously or be induced by MUTAGENS.
Within a eukaryotic cell, a membrane-limited body which contains chromosomes and one or more nucleoli (CELL NUCLEOLUS). The nuclear membrane consists of a double unit-type membrane which is perforated by a number of pores; the outermost membrane is continuous with the ENDOPLASMIC RETICULUM. A cell may contain more than one nucleus. (From Singleton & Sainsbury, Dictionary of Microbiology and Molecular Biology, 2d ed)
Enzymes that catalyze DNA template-directed extension of the 3'-end of an RNA strand one nucleotide at a time. They can initiate a chain de novo. In eukaryotes, three forms of the enzyme have been distinguished on the basis of sensitivity to alpha-amanitin, and the type of RNA synthesized. (From Enzyme Nomenclature, 1992).
A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine).
Proteins, usually glycoproteins, found in the viral envelopes of a variety of viruses. They promote cell membrane fusion and thereby may function in the uptake of the virus by cells.
Infections produced by oncogenic viruses. The infections caused by DNA viruses are less numerous but more diverse than those caused by the RNA oncogenic viruses.
The relationships of groups of organisms as reflected by their genetic makeup.
Deliberate stimulation of the host's immune response. ACTIVE IMMUNIZATION involves administration of ANTIGENS or IMMUNOLOGIC ADJUVANTS. PASSIVE IMMUNIZATION involves administration of IMMUNE SERA or LYMPHOCYTES or their extracts (e.g., transfer factor, immune RNA) or transplantation of immunocompetent cell producing tissue (thymus or bone marrow).
Genetically engineered MUTAGENESIS at a specific site in the DNA molecule that introduces a base substitution, or an insertion or deletion.
Test for tissue antigen using either a direct method, by conjugation of antibody with fluorescent dye (FLUORESCENT ANTIBODY TECHNIQUE, DIRECT) or an indirect method, by formation of antigen-antibody complex which is then labeled with fluorescein-conjugated anti-immunoglobulin antibody (FLUORESCENT ANTIBODY TECHNIQUE, INDIRECT). The tissue is then examined by fluorescence microscopy.
The type species of LYMPHOCRYPTOVIRUS, subfamily GAMMAHERPESVIRINAE, infecting B-cells in humans. It is thought to be the causative agent of INFECTIOUS MONONUCLEOSIS and is strongly associated with oral hairy leukoplakia (LEUKOPLAKIA, HAIRY;), BURKITT LYMPHOMA; and other malignancies.
A species of the genus MACACA inhabiting India, China, and other parts of Asia. The species is used extensively in biomedical research and adapts very well to living with humans.
Lymphocytes responsible for cell-mediated immunity. Two types have been identified - cytotoxic (T-LYMPHOCYTES, CYTOTOXIC) and helper T-lymphocytes (T-LYMPHOCYTES, HELPER-INDUCER). They are formed when lymphocytes circulate through the THYMUS GLAND and differentiate to thymocytes. When exposed to an antigen, they divide rapidly and produce large numbers of new T cells sensitized to that antigen.
The arrangement of two or more amino acid or base sequences from an organism or organisms in such a way as to align areas of the sequences sharing common properties. The degree of relatedness or homology between the sequences is predicted computationally or statistically based on weights assigned to the elements aligned between the sequences. This in turn can serve as a potential indicator of the genetic relatedness between the organisms.
A species of RESPIROVIRUS also called hemadsorption virus 2 (HA2), which causes laryngotracheitis in humans, especially children.
A family of non-enveloped viruses infecting mammals (MASTADENOVIRUS) and birds (AVIADENOVIRUS) or both (ATADENOVIRUS). Infections may be asymptomatic or result in a variety of diseases.
Retroviral proteins, often glycosylated, coded by the envelope (env) gene. They are usually synthesized as protein precursors (POLYPROTEINS) and later cleaved into the final viral envelope glycoproteins by a viral protease.
RNA consisting of two strands as opposed to the more prevalent single-stranded RNA. Most of the double-stranded segments are formed from transcription of DNA by intramolecular base-pairing of inverted complementary sequences separated by a single-stranded loop. Some double-stranded segments of RNA are normal in all organisms.
A species of LEPORIPOXVIRUS causing subcutaneous localized swellings in rabbits, usually on the feet.
A DNA-binding protein that consists of 5 polypeptides and plays an essential role in DNA REPLICATION in eukaryotes. It binds DNA PRIMER-template junctions and recruits PROLIFERATING CELL NUCLEAR ANTIGEN and DNA POLYMERASES to the site of DNA synthesis.
The degree of similarity between sequences of amino acids. This information is useful for the analyzing genetic relatedness of proteins and species.
A multistage process that includes cloning, physical mapping, subcloning, determination of the DNA SEQUENCE, and information analysis.
The restriction of a characteristic behavior, anatomical structure or physical system, such as immune response; metabolic response, or gene or gene variant to the members of one species. It refers to that property which differentiates one species from another but it is also used for phylogenetic levels higher or lower than the species.
A species of ORTHOPOXVIRUS infecting mice and causing a disease that involves internal organs and produces characteristic skin lesions.
The naturally occurring or experimentally induced replacement of one or more AMINO ACIDS in a protein with another. If a functionally equivalent amino acid is substituted, the protein may retain wild-type activity. Substitution may also diminish, enhance, or eliminate protein function. Experimentally induced substitution is often used to study enzyme activities and binding site properties.
An indole-dione that is obtained by oxidation of indigo blue. It is a MONOAMINE OXIDASE INHIBITOR and high levels have been found in urine of PARKINSONISM patients.
Pneumovirus infections caused by the RESPIRATORY SYNCYTIAL VIRUSES. Humans and cattle are most affected but infections in goats and sheep have been reported.
A species of POLYOMAVIRUS apparently infecting over 90% of children but not clearly associated with any clinical illness in childhood. The virus remains latent in the body throughout life and can be reactivated under certain circumstances.
The developmental entity of a fertilized chicken egg (ZYGOTE). The developmental process begins about 24 h before the egg is laid at the BLASTODISC, a small whitish spot on the surface of the EGG YOLK. After 21 days of incubation, the embryo is fully developed before hatching.
Biological properties, processes, and activities of VIRUSES.
Viruses which produce a mottled appearance of the leaves of plants.
Carbon-containing phosphonic acid compounds. Included under this heading are compounds that have carbon bound to either OXYGEN atom or the PHOSPHOROUS atom of the (P=O)O2 structure.
The part of a cell that contains the CYTOSOL and small structures excluding the CELL NUCLEUS; MITOCHONDRIA; and large VACUOLES. (Glick, Glossary of Biochemistry and Molecular Biology, 1990)
The process by which a DNA molecule is duplicated.
Inactivation of viruses by non-immune related techniques. They include extremes of pH, HEAT treatment, ultraviolet radiation, IONIZING RADIATION; DESICCATION; ANTISEPTICS; DISINFECTANTS; organic solvents, and DETERGENTS.
Phase of the CELL CYCLE following G1 and preceding G2 when the entire DNA content of the nucleus is replicated. It is achieved by bidirectional replication at multiple sites along each chromosome.
Proteins that bind to RNA molecules. Included here are RIBONUCLEOPROTEINS and other proteins whose function is to bind specifically to RNA.
The property of objects that determines the direction of heat flow when they are placed in direct thermal contact. The temperature is the energy of microscopic motions (vibrational and translational) of the particles of atoms.
Recombinant DNA vectors encoding antigens administered for the prevention or treatment of disease. The host cells take up the DNA, express the antigen, and present it to the immune system in a manner similar to that which would occur during natural infection. This induces humoral and cellular immune responses against the encoded antigens. The vector is called naked DNA because there is no need for complex formulations or delivery agents; the plasmid is injected in saline or other buffers.
A single chain of deoxyribonucleotides that occurs in some bacteria and viruses. It usually exists as a covalently closed circle.
Recombinant proteins produced by the GENETIC TRANSLATION of fused genes formed by the combination of NUCLEIC ACID REGULATORY SEQUENCES of one or more genes with the protein coding sequences of one or more genes.
The type species of PNEUMOVIRUS and an important cause of lower respiratory disease in infants and young children. It frequently presents with bronchitis and bronchopneumonia and is further characterized by fever, cough, dyspnea, wheezing, and pallor.
The sum of the weight of all the atoms in a molecule.
A species of RESPIROVIRUS frequently isolated from small children with pharyngitis, bronchitis, and pneumonia.
A phenomenon in which infection by a first virus results in resistance of cells or tissues to infection by a second, unrelated virus.
The type species of PARAPOXVIRUS which causes a skin infection in natural hosts, usually young sheep. Humans may contract local skin lesions by contact. The virus apparently persists in soil.
A non-metabolizable galactose analog that induces expression of the LAC OPERON.
The major interferon produced by mitogenically or antigenically stimulated LYMPHOCYTES. It is structurally different from TYPE I INTERFERON and its major activity is immunoregulation. It has been implicated in the expression of CLASS II HISTOCOMPATIBILITY ANTIGENS in cells that do not normally produce them, leading to AUTOIMMUNE DISEASES.
The ability of viruses to resist or to become tolerant to chemotherapeutic agents or antiviral agents. This resistance is acquired through gene mutation.
Proteins encoded by the GAG GENE of the HUMAN IMMUNODEFICIENCY VIRUS.
A species of POLYOMAVIRUS, originally isolated from the brain of a patient with progressive multifocal leukoencephalopathy. The patient's initials J.C. gave the virus its name. Infection is not accompanied by any apparent illness but serious demyelinating disease can appear later, probably following reactivation of latent virus.
An inheritable change in cells manifested by changes in cell division and growth and alterations in cell surface properties. It is induced by infection with a transforming virus.
The type species of RESPIROVIRUS in the subfamily PARAMYXOVIRINAE. It is the murine version of HUMAN PARAINFLUENZA VIRUS 1, distinguished by host range.
Sites on an antigen that interact with specific antibodies.
Widely used technique which exploits the ability of complementary sequences in single-stranded DNAs or RNAs to pair with each other to form a double helix. Hybridization can take place between two complimentary DNA sequences, between a single-stranded DNA and a complementary RNA, or between two RNA sequences. The technique is used to detect and isolate specific sequences, measure homology, or define other characteristics of one or both strands. (Kendrew, Encyclopedia of Molecular Biology, 1994, p503)
Proteins conjugated with nucleic acids.
Naturally occurring or experimentally induced animal diseases with pathological processes sufficiently similar to those of human diseases. They are used as study models for human diseases.
The level of protein structure in which combinations of secondary protein structures (alpha helices, beta sheets, loop regions, and motifs) pack together to form folded shapes called domains. Disulfide bridges between cysteines in two different parts of the polypeptide chain along with other interactions between the chains play a role in the formation and stabilization of tertiary structure. Small proteins usually consist of only one domain but larger proteins may contain a number of domains connected by segments of polypeptide chain which lack regular secondary structure.
The type species of the FLAVIVIRUS genus. Principal vector transmission to humans is by AEDES spp. mosquitoes.
Viruses that produce tumors.
The entering of cells by viruses following VIRUS ATTACHMENT. This is achieved by ENDOCYTOSIS, by direct MEMBRANE FUSION of the viral membrane with the CELL MEMBRANE, or by translocation of the whole virus across the cell membrane.
Agents used to treat AIDS and/or stop the spread of the HIV infection. These do not include drugs used to treat symptoms or opportunistic infections associated with AIDS.
The type species of VARICELLOVIRUS causing CHICKENPOX (varicella) and HERPES ZOSTER (shingles) in humans.
A major core protein of the human immunodeficiency virus encoded by the HIV gag gene. HIV-seropositive individuals mount a significant immune response to p24 and thus detection of antibodies to p24 is one basis for determining HIV infection by ELISA and Western blot assays. The protein is also being investigated as a potential HIV immunogen in vaccines.
DNA sequences that form the coding region for proteins associated with the viral core in retroviruses. gag is short for group-specific antigen.
Glycoproteins found on the membrane or surface of cells.
The capacity of a normal organism to remain unaffected by microorganisms and their toxins. It results from the presence of naturally occurring ANTI-INFECTIVE AGENTS, constitutional factors such as BODY TEMPERATURE and immediate acting immune cells such as NATURAL KILLER CELLS.
... in the J segment of the Wyeth strain vaccinia virus. Elimination of TK from the JX-594 genome restricts viral replication to ... Oncolytic viruses developed by Jennerex are based on the vaccinia virus. Pexa-Vec is an engineered oncolytic virus that ... to select transgenes to include into the viral genome, and to optimize viral infection and/or replication selectivity through ... Because JX-594 is based on the Wyeth strain vaccinia virus that is commonly used for vaccination, it is well tolerated by rats ...
Transgene uses three types of vectors: Modified vaccinia Ankara (MVA); Vaccinia virus and adenovirus. TG4010, a specific active ... lysis of cancer cells through viral replication, the reduction of the blood supply to tumors through vascular targeting and ... The engineered oncolytic vaccinia virus is armed with the immunostimulatory cytokine GM-CSF and is designed to selectively ... The therapy is based on a recombinant vaccinia virus expressing the MUC1 antigen and the human cytokine, interleukin-2 (IL2). ...
... again suggesting that the binding between sulfatide and hemagglutinin facilitates IAV replication. Vaccinia virus is closely ... Experimentation with sulfatide has shown that it has involvement in several viral infections, including HIV-1, Influenza A ... The vaccinia virus has been shown to be able to bind to sulfatide through the L5 and A27 membrane proteins on the virus. It has ... Influenza A virus, Hepatitis C and Vaccinia virus. Additionally, overexpression of sulfatide has been linked to epilepsy and ...
It appeared to Kempe, that the presence of the antibodies blocked viral replication and therefore a transfusion of antibodies ... Vaccinia virus Eczema vaccinatum Gamma globulin Smallpox Vaccine: Contraindications, Administration, and Adverse Reactions CDC ... Humoral and cell-mediated immune responses in humans before and after revaccination with vaccinia virus. Infect Immun. 1978;19: ... Vaccinia immune globulin (VIG) is made from the pooled blood of individuals who have been inoculated with the smallpox vaccine ...
About one third of the genome is not necessary for the viral replication itself. These viral products interfere with the host ... is a protein expressed by vaccinia virus. Vaccinia virus is member of Orthopoxvirus family. These viruses contain approximately ... The Copenhagen strain of vaccinia virus only has a truncated version of this protein. Vaccinia virus encodes two more serpin - ... "Vaccinia virus serpin B13R (SPI-2) inhibits interleukin-1beta-converting enzyme and protects virus-infected cells from TNF- and ...
These enzymes also exist in the genomes of certain viruses (E.g. HSV, vaccinia) and allow viral replication in quiescent(non- ... A number of viruses including adenovirus, reovirus, measles, herpes simplex, Newcastle disease virus, and vaccinia have been ... Kuruppu D, Tanabe KK (May 2005). "Viral oncolysis by herpes simplex virus and other viruses". Cancer Biology & Therapy. 4 (5): ... This approach has been used successfully preclinically with adenovirus, measles virus and vaccinia virus. Talimogene ...
"Development of Vaccinia Reporter Viruses for Rapid, High Content Analysis of Viral Function at All Stages of Gene Expression". ... The results of this study provided useful information for the tracking of viral activity and replication. At this time, there ... "Vaccinia Virus Infection & Temporal Analysis of Virus Gene Expression". JoVE. Retrieved March 17, 2013. Chancellor, Jeffery C ... The researchers utilize fluorescent protein-based reporters to monitor and analyze the function of the Vaccinia virus. This ...
... virus Camelpox virus Cowpox virus Ectromelia virus Monkeypox virus Raccoonpox virus Skunkpox virus Taterapox virus Vaccinia ... Viral replication is cytoplasmic. Entry into the host cell is achieved by attachment of the viral proteins to host ... Others, such as ectromelia and camelpox viruses, are highly host-specific. Vaccinia virus, maintained in vaccine institutes and ... through the use of Vaccinia virus as a vaccine. The most recently described species is the Alaskapox virus, first isolated in ...
... is able to inhibit herpesvirus and vaccinia virus replication in cells during tissue culture. However, cytarabine ... When used as an antiviral, cytarabine-5´-triphosphate functions by inhibiting viral DNA synthesis. ... which require DNA replication for mitosis, are therefore most affected. Cytosine arabinoside also inhibits both DNA and RNA ...
... and its ability to enervate RNA virus transcrip-tion and replication in vitro. Fish Shellfish Immunol 92:655-666 Viral ... A vaccinia virus free reverse genetic system for Great Lakes VHSV (Genotype IVb) was developed by a research group from the USA ... Even though it has been demonstrated that the NV gene is not necessary for viral replication, it is highly essential for viral ... Viral hemorrhagic septicemia virus and infectious hematopoietic necrosis virus". Journal of Virology. 84 (19): 10038-50. doi: ...
... and to optimize viral infection and/or replication selectively through targeted mutations. Oncolytic Virus could have 3- ... an Oncolytic and Immunotherapeutic Vaccinia Virus, in Pediatric Cancer Patients Un virus contre le cancer 25 March 2012, Radio ... SOLVE™ (Selective Oncolytic Vaccinia Engineering) platform: This platform is used to optimize virus targeting to specific ... Novel oncolytic viruses in SillaJen pipeline are engineered through the Selective Oncolytic Vaccinia Engineering (SOLVE) ...
This is mostly shown for plant RNA viruses. Viroplasm is the location within the infected cell where viral replication and ... Viroplasms have been found in the cauliflower mosaic virus, rotavirus, vaccinia virus and the rice dwarf virus. These appear ... Szajner; Weisberg, AS; Wolffe, EJ; Moss, B (2001). "Vaccinia virus A30L protein is required for association of viral membranes ... Viral evolution Viral replication Novoa, R. R.; Calderita, G.; Arranz, R.; Fontana, J.; Granzow, H.; Risco, C. (Feb 2005). " ...
Replication and Transcription: The replication and transcription of the viral genome occur in the cytoplasm. Genome replication ... Unlike the HA of other vaccinia-like viruses, the HA of RCN did not cross-react with monkeypox virus HA. Though RPV is a close ... Once uncoated, the viral DNA is expressed and replication follows. Replication of the RCN genome occurs through the strand ... The sera partially cross-reacted with a vaccinia virus HA preparation, suggesting a close relation between the viruses. ...
... human metapneumovirus and vaccinia virus. His group is particularly known for their work on antibody recognition of viral ... Sapparapu G, Fernandez E... Crowe JE (2016). Neutralizing human antibodies prevent Zika virus replication and fetal disease in ... in particular influenza virus, HIV, dengue virus, respiratory syncytial virus, rotavirus, ... James Crowe's research has focused on adaptive immune responses to various viral pathogens, ...
... to select transgenes to include into the viral genome, and to optimize viral infection and/or replication selectively through ... "Hepatocellular Carcinoma Study Comparing Vaccinia Virus Based Immunotherapy Plus Sorafenib vs Sorafenib Alone - Full Text View ... "First-in-man Study of Western Reserve Strain Oncolytic Vaccinia Virus: Safety, Systemic Spread, and Antitumor Activity". ... Pexa-Vec (JX-594) was developed using the SOLVE (Selective Oncolytic Vaccinia Engineering) platform. This platform may be used ...
Notable poxviruses include Variola virus, which causes smallpox, and Vaccinia virus, which is used as the vaccine against ... Virophages replicate by hijacking the replication apparati of giant viruses, thereby suppressing the number of giant virus ... From there, based on phylogenetic analysis of the viral DNA polymerase and other characteristics, eukaryotic viruses in ... which are satellite viruses of giant viruses, transpovirons, which are linear plasmid-like DNA molecules found in giant viruses ...
It is a nucleoside analogue, a modified form of deoxyuridine, similar enough to be incorporated into viral DNA replication, but ... as well as for prevention and treatment of vaccinia virus infections of the eye. A Cochrane Systematic Review showed that ... thus interfering with viral DNA replication. Trifluridine passes the cornea and is found in the aqueous humour. Systemic ... Trifluridine eye drops are used for the treatment of keratitis and keratoconjunctivitis caused by the herpes simplex virus ...
E5R protein from Chordopoxvirus virosomes, which is found in cytoplasmic sites of viral DNA replication. Several proteins of ... "Identification by mass spectroscopy of three major early proteins associated with virosomes in vaccinia virus-infected cells". ... NACC1, a novel member of the POZ/BTB (Pox virus and Zinc finger/Bric-a-bracTramtrack Broad complex), but which varies from ... protein and in polydnaviral proteins also suggests a possible role in the organisation of viral DNA during replication or ...
Each virion sets up a region in the cytoplasm, called a 'viral factory' where DNA replication, transcription, and translation ... Over 100 of these genes are conserved in other viruses from the poxvirus family, such as Variola virus and Vaccinia virus. The ... Because of this, the virus must bring all necessary enzymes for replication with it or encode the enzymes in its genome. The ... Therefore, because the host cell proteins for DNA replication are present inside the nucleus, this virus has to bring or encode ...
Orthopox: smallpox virus (variola), vaccinia virus, cowpox virus, monkeypox virus, rabbitpox virus; Parapox: orf virus, ... Modern viral classification is based on phenotypic characteristics; morphology, nucleic acid type, mode of replication, host ... Vaccinia virus is most closely related to CPV-GRI-90. The prototypical poxvirus is vaccinia virus, known for its role in the ... tanapox virus, yaba monkey tumor virus; Molluscipox: molluscum contagiosum virus (MCV). The most common are vaccinia (seen on ...
B-type inclusions are the sites of viral replication and are found in all poxvirus-infected cells, unlike A-type inclusions ... "Variola Virus". Archived from the original on 23 January 2009. Retrieved 2009-01-02. Esiri, Margaret M.; Booss, John (2003). ... smallpox or vaccinia). In cells stained with eosin, they appear as pink blobs in the cytoplasm of affected epithelial cells. ... Viral Encephalitis in Humans. Washington, D.C: ASM Press. pp. 117. ISBN 1-55581-240-6. Binns, Matthew M.; Smith, Geoffrey L.; ...
... which suggests that viral mRNA synthesis and crucial steps that occur during viral replication are not necessary for induction ... indicated that this interaction induced an antiviral state that strongly inhibited vaccinia and vesicular stomatitis virus (VSV ... Virus particles can range between 70-80 nm. Morphologically, the virus is a double stranded RNA virus that is composed of ten ... The main site of viral replication was observed in the enteric tract. A different study of early pathogenesis in chicks ...
Tolonen N, Doglio L, Schleich S, Krijnse Locker J (1 July 2001). "Vaccinia Virus DNA Replication Occurs in Endoplasmic ... and vaccinia was subsequently recognized as a separate viral species. Whole-genome sequencing has revealed that vaccinia is ... vaccinia gangrenosum, vaccinia necrosum) Roseola vaccinia Vaccinia virus is closely related to the virus that causes cowpox; ... The most common notion is that vaccinia virus, cowpox virus, and variola virus (the causative agent of smallpox) were all ...
... viral vector - virotherapy - virtual colonoscopy - Virulizin - virus replication cycle - virus-neutralizing antibody - ... vaccinia CEA vaccine - vaginal cancer - vaginal melanoma-vaginal tumors - valacyclovir - valdecoxib - valerian - Valeriana ... Epstein-Barr virus - EPT - ER - ER+ - ER- - ERA-923 - erb-38 immunotoxin - ErbB1 - ERCP - erlotinib - ERT - ERUS - erythema - ... Oncolytic virus - Onconase - ondansetron - ONYX-015 - oophorectomy - open biopsy - open colectomy - open label study - opioid ...
... adenovirus simian virus 40, vaccinia virus, reovirus, poliovirus and herpes simplex virus as well as numerous bacteriophages.[ ... Transduction is the process by which foreign DNA is introduced into a cell by a virus or viral vector. Transduction is a common ... Viruses are capsid-encoding organisms composed of proteins and nucleic acids that can self-assemble after replication in a host ... Seto, Donald (30 November 2010). "Viral Genomics and Bioinformatics". Viruses. 2 (12): 2587-2593. doi:10.3390/v2122587.. ...
It is a recombinant, replication-competent vaccine consisting of vesicular stomatitis virus (VSV) genetically engineered so ... Mvabea, the second dose of the Zabdeno/Mvabea Ebola vaccine, is a modified vaccinia Ankara vector, a type of poxvirus. Both ... and Sendai virus, as well as influenza virus and measles virus. Human clinical trials were conducted for viral vector vaccines ... Viral vector vaccines use a modified version of one virus as a vector to deliver to a cell a nucleic acid coding for an antigen ...
... while granzyme B cleaves viral proteins to inhibit viral activation and replication. The granzymes bind directly to the nucleic ... December 2011). "Granzyme B inhibits vaccinia virus production through proteolytic cleavage of eukaryotic initiation factor 4 ... Granzymes also kill bacteria and inhibit viral replication. In NK cells and T cells, granzymes are packaged in cytotoxic ... Test on mice have shown that granzyme A and B might not have a direct link to controlling viral infections, but helping ...
... to fund a vaccine against Lassa virus via replication-competent vesicular stomatitis viral vector technology. In June 2018, US$ ... using a recombinant modified vaccinia Ankara viral vector technology. In September 2018, US$19 million to Janssen Pharmaceutica ... the Nipah virus, the Lassa fever virus, and the Rift Valley fever virus, as well as the Chikungunya virus and the hypothetical ... Nipah virus, Lassa fever virus, and Rift Valley fever virus, as well as Chikungunya virus, and the WHO's Disease X. CEPI ...
Viral replication is cytoplasmic. Entry into the host cell is achieved by attachment of the viral proteins to host ... It is the most common cause of pox disease in pigs, with vaccinia virus being the next most common cause of outbreaks. It is a ... "Viral Zone". ExPASy. Retrieved 15 June 2015. CS1 maint: discouraged parameter (link) ICTV. "Virus Taxonomy: 2014 Release". ... The assembly of progeny virions starts in cytoplasmic viral factories and produces a spherical, immature particle. This virus ...
During the 19th century, the cowpox virus used for smallpox vaccination was replaced by vaccinia virus. Vaccinia is in the same ... and are the sites of viral replication. Guarnieri bodies are readily identified in skin biopsies stained with hematoxylin and ... It contains live vaccinia virus, cloned from the same strain used in an earlier vaccine, Dryvax. While the Dryvax virus was ... The current formulation of smallpox vaccine is a live virus preparation of infectious vaccinia virus. The vaccine is given ...
Examples of viruses that undergo this process are herpes simplex virus, human immunodeficiency virus, and vaccinia virus.[44] ... VirusEdit. A variety of prevention and treatment options exist for some viral pathogens. Vaccines are one common and effective ... biology proposes that many pathogens evolve an optimal virulence at which the fitness gained by increased replication rates is ... Vaccines exist for viruses such as the measles, mumps, and rubella viruses and the influenza virus.[30] Some viruses such as ...
When the virus enters into lytic replication, thousands of virus particles can be made from a single cell, which usually ... The primary viral protein responsible for the switch between latent and lytic replication is known as the ORF50 Replication ... When the virus reactivates into lytic replication, it is believed that the virus genome is replicated as a continuous linear ... "lytic replication"). Various signals such as inflammation may provoke the virus to enter into lytic replication. When lytic ...
"Cloning the vaccinia virus genome as a bacterial artificial chromosome in Escherichia coli and recovery of infectious virus in ... for plasmid replication and regulation of copy number.. parA and parB. for partitioning F plasmid DNA to daughter cells during ... as transfection of the BAC construct into host cells is sufficient to initiate viral infection. The infectious property of ... The genomes of several large DNA viruses and RNA viruses have been cloned as BACs. These constructs are referred to as " ...
Replication of viruses involves primarily multiplication of the genome. Replication involves synthesis of viral messenger RNA ( ... Vaccinia virus, by optical microscopy after staining it. Vaccinia was not known to be a virus at that time. (Buist J.B. ... I: dsDNA viruses. II: ssDNA viruses. III: dsRNA viruses. IV: (+)ssRNA viruses. V: (−)ssRNA viruses. VI: ssRNA-RT viruses. VII: ... A virus has either a DNA or an RNA genome and is called a DNA virus or an RNA virus, respectively. The vast majority of viruses ...
... is a viral infection caused by the herpes simplex virus.[1] Infections are categorized based on the part of the ... Topical Tenofovir, a Microbicide Effective against HIV, Inhibits Herpes Simplex Virus-2 Replication Archived 2017-04-09 at the ... For the virus that causes herpes simplex, see Herpes simplex virus. For all types of herpes viruses, see Herpesviridae. ... "Viral entry mechanisms: cellular and viral mediators of herpes simplex virus entry". FEBS Journal. 276 (24): 7228-36. doi ...
... with viral replication[2] by protecting cells from virus infections. IFNs also have various other functions: they activate ... Nagano Y, Kojima Y (October 1954). "[Immunizing property of vaccinia virus inactivated by ultraviolets rays]". Comptes Rendus ... Viruses that inhibit IFN signaling include Japanese Encephalitis Virus (JEV), dengue type 2 virus (DEN-2) and viruses of the ... Some viruses escape the anti-viral activities of interferons by gene (and thus protein) mutation. The H5N1 influenza virus, ...
The virus infects the cells in the epidermal layer of the skin. The initial viral replication occurs at the entry site in the ... These less common forms can be potentially more serious.[2] Anti-viral treatments will not have an effect in non-viral cases. ... Infection with either type of the HSV viruses occurs in the following way: First, the virus comes in contact with damaged skin ... Infectious skin disease: Viral cutaneous conditions, including viral exanthema (B00-B09, 050-059) ...
Replication of viruses involves primarily multiplication of the genome. Replication involves synthesis of viral messenger RNA ( ... Vaccinia virus, by optical microscopy after staining it. Vaccinia was not known to be a virus at that time. (Buist J.B. ... A virus has either a DNA or an RNA genome and is called a DNA virus or an RNA virus, respectively. The vast majority of viruses ... viral protein synthesis, possible assembly of viral proteins, then viral genome replication mediated by early or regulatory ...
The importance of IFNγ in the immune system stems in part from its ability to inhibit viral replication directly, and most ... response to virus. • positive regulation of membrane protein ectodomain proteolysis. • positive regulation of epithelial cell ... defense response to virus. • positive regulation of interleukin-1 beta secretion. • positive regulation of neuron ... IFNγ, or type II interferon, is a cytokine that is critical for innate and adaptive immunity against viral, some bacterial and ...
Camelpox virus Cowpox virus Ectromelia virus Monkeypox virus Raccoonpox virus Skunkpox virus Taterapox virus Vaccinia virus ... Viral replication is cytoplasmic. Entry into the host cell is achieved by attachment of the viral proteins to host ... Canarypox virus Fowlpox virus Juncopox virus Mynahpox virus Pigeonpox virus Psittacinepox virus Quailpox virus Sparrowpox virus ... Nile crocodilepox virus Genus: Leporipoxvirus Hare fibroma virus Myxoma virus Rabbit fibroma virus Squirrel fibroma virus Genus ...
An example of this is the pox virus vaccinia which encoded a viral growth factor similar that is very similar to the human ... Antigenic drift: point mutations that occur through imperfect replication of the viral genome. All viruses exhibit genetic ... Flaviviridae is a family of viruses that encompasses well known viruses such as West Nile virus and Dengue virus. The genus ... As the viral cells go through replication they reassort and the genes of the two species get mixed up and make 256 new ...
... which suggests that viral mRNA synthesis and crucial steps that occur during viral replication are not necessary for induction ... indicated that this interaction induced an antiviral state that strongly inhibited vaccinia and vesicular stomatitis virus (VSV ... Virus particles can range between 70-80 nm. Morphologically, the virus is a double stranded RNA virus that is composed of ten ... The main site of viral replication was observed in the enteric tract.[13] A different study of early pathogenesis in chicks ...
Viral life cycle. *Viral entry. *Viral replication. *Viral shedding. *Virus latency. *Viroplasm ... Vaccinia virus, by optical microscopy after staining it. Vaccinia was not known to be a virus at that time. Buist, J.B. (1887 ... The virus was later shown to be a previously unrecognised herpes virus, which is now called Epstein-Barr virus.[55] ... The importance of tobacco mosaic virus in the history of viruses cannot be overstated. It was the first virus to be discovered ...
... to retain the differentiating host keratinocyte in a state that is favourable to the amplification of viral genome replication ... DNA virus. HBV (B). RNA virus. CBV. HAV (A). HCV (C). HDV (D). HEV (E). HGV (G). ... DNA virus. JCV Progressive multifocal leukoencephalopathy. RNA virus. MeV Subacute sclerosing panencephalitis. LCV Lymphocytic ... Infectious skin disease: Viral cutaneous conditions, including viral exanthema (B00-B09, 050-059) ...
The first virus to be used as a vaccine vector was the vaccinia virus in 1984 as a way to protect chimpanzees against hepatitis ... In gene therapy a gene that is intended for delivery is packaged into a replication-deficient viral particle to form a viral ... DNA-based viral vectors include Adenoviridae, adeno-associated virus and herpes simplex virus. Several of the methods used to ... Viruses used for gene therapy to date include retrovirus, adenovirus, adeno-associated virus and herpes simplex virus. However ...
... iodide symporter to facilitate deep tissue imaging does not alter oncolytic or replication capability of a novel vaccinia virus ... "Genelux Announces Positive Phase 1 Data for Viral-Based Cancer Therapy". Drug Discovery & Development. Clinical Trials & ... 2013). "Vaccinia virus-mediated melanin production allows MR and optoacoustic deep tissue imaging and laser-induced ... The dogs are treated with V-VET1, a non-genetically modified vaccinia virus isolate (laboratory name LIVP6.1.1) with an ...
This stage of viral replication can be inhibited in two ways: Using agents which mimic the virus-associated protein (VAP) and ... "Assembly of vaccinia virus: effects of rifampin on the intracellular distribution of viral protein p65". J. Virol. 68 (2): 1103 ... Replication of viral components using host-cell machinery. Assembly of viral components into complete viral particles. Release ... One anti-viral strategy is to interfere with the ability of a virus to infiltrate a target cell. The virus must go through a ...
Such replication-impaired viruses unite many of the advantages of both live and killed virus vaccines, and are much less likely ... Using HSV-2, which causes genital herpes, they disabled the virus by deleting the viral gene encoding the membrane protein ... of immunoglobulin G Fc receptors by recombinant vaccinia viruses expressing glycoproteins E and I of herpes simplex virus type ... His research in the early 1970s was in the field of plant viruses, including tobacco rattle virus and tobacco necrosis virus, ...
... including attenuated viruses, viral proteins, peptides, and recombinant vaccinia vectors expressing the Friend virus gene. In a ... "Murine leukemia virus (MLV) replication monitored with fluorescent proteins". Virology Journal. 1: 14. doi:10.1186/1743-422X-1- ... The Friend virus (FV) is a strain of murine leukemia virus. The Friend virus has been used for both immunotherapy and vaccines ... The genomes of exogenous and endogenous murine leukemia viruses have been fully sequenced. The viral genome is a single ...
... of tumor cells as well as decreased ability of tumor cells to fight off viruses make them advantageous for viral replication ... and vaccinia virus, but other viruses include measles virus, coxsackievirus, polio virus, newcastle disease virus, and more. ... There are three main branches of virotherapy: anti-cancer oncolytic viruses, viral vectors for gene therapy and viral ... is another form of viral immunotherapy that uses viruses to genetically engineer immune cells to kill cancer cells. Viruses ...
Our data indicate that B12 is not a global repressor, but inhibits vaccinia replication in the absence of the B1 kinase. The ... However, the parallel B12 pathway to restrict virus replication is less clear. Together, our studies of B1 and B12 present ... We began by constructing and characterizing the first B1 deletion virus (ΔB1). Then using this virus, we tested the hypothesis ... our characterization of the adapted viruses reveals that mutations correlating with a loss of function of the vaccinia B12 ...
... an oncolytic vaccinia virus with interferon-dependent cancer selectivity that allows tumor-specific replication; it also ... Viral replication Is the Subject Area "Viral replication" applicable to this article? Yes. No. ... Vaccinia virus Is the Subject Area "Vaccinia virus" applicable to this article? Yes. No. ... Viral gene expression Is the Subject Area "Viral gene expression" applicable to this article? Yes. No. ...
Dominance and diversity in the primary human CD4 T cell response to replication-competent vaccinia virus. J Immunol. 2007;178( ... Cellular responses to viral infection in humans: lessons from Epstein-Barr virus. Annu Rev Immunol. 2007;25:587-617.. View this ... Application to vaccinia virus. Participant 9 from a previous report (47) was re-vaccinated with vaccinia 20 months prior to ... Enhanced expression of HIV antigens and improved cross-presentation by replication competent recombinant vaccinia virus vector ...
Is Required for High Efficiency Viral Replication * Modified Vaccinia Virus Ankara Triggers Type I IFN Production in Murine ... and monkeypox virus are important human pathogens [1]-[3]. Modified vaccinia virus Ankara (MVA) is an attenuated vaccinia virus ... 2005) Role of viral factor E3L in modified vaccinia virus ankara infection of human HeLa Cells: regulation of the virus life ... Viruses and cell lines. The WR strain of vaccinia virus was propagated and virus titers were determined on BSC40 (African green ...
About one third of the genome is not necessary for the viral replication itself. These viral products interfere with the host ... is a protein expressed by vaccinia virus. Vaccinia virus is member of Orthopoxvirus family. These viruses contain approximately ... The Copenhagen strain of vaccinia virus only has a truncated version of this protein. Vaccinia virus encodes two more serpin - ... "Vaccinia virus serpin B13R (SPI-2) inhibits interleukin-1beta-converting enzyme and protects virus-infected cells from TNF- and ...
... that a single dose of a replication-deficient MVA vector can confer full protection against a lethal challenge with ML29 virus. ... When expressed together, GP and Z form Virus-Like Particles (VLPs) in cell culture. Immunogenicity and efficacy of GEO-LM01 was ... Constructed in the Modified Vaccinia Ankara (MVA) vector, GEO-LM01 expresses the glycoprotein precursor (GPC) and zinc-binding ... a Mopeia/Lassa reassortant virus, delivered directly into the brain. In contrast, all control animals died within one week. The ...
... each containing one of the four viral genes, into cell cultures previously infected with a vaccinia virus recombinant encoding ... In influenza virus-infected cells however, CAT activity was detected only when the CAT RNA contained the viral promoter at the ... When a naked negative-sense influenza virus-like CAT RNA was transfected into cells expressing the four influenza virus ... Expression of the four influenza virus core proteins (nucleoprotein, PA, PB1 and PB2) was performed by transfection of four ...
Vaccinia-virus-induced cellular contractility facilitates the subcellular localization of the viral replication sites. ... A vaccinia virus lacking A10L: viral core proteins accumulate on structures derived from the endoplasmic reticulum. ... Characterization of vaccinia virus intracellular cores: implications for viral uncoating and core structure. ... Entry of the two infectious forms of vaccinia virus at the plasma membane is signaling-dependent for the IMV but not the EEV. ...
Although the exact origins of vaccinia virus are uncertain, vaccinia may represent a hybrid of the variola and cowpox viruses. ... Vaccination with vaccinia virus has been directly responsible for the successful eradication of smallpox (variola). ... The initial proteins synthesized are used to further uncoat the virus and to begin the process of viral DNA replication. The ... Replication-defective attenuated vaccinia viruses. Modified versions of vaccinia virus have been developed for use as ...
Biodistribution of the viruses. For examination of viral replication and viral yields in tissues, nude mice were injected i.p. ... Vaccinia virus. In: Hernáiz Driever P, Rabkin SD, editors. Replication-competent viruses for cancer therapy. Monogr Virol. Vol ... Vaccinia viruses. All vaccinia viruses used in this study are derivatives of the WR strain. The pseudo-wild-type vF13L+, a WR ... and VGF-deleted vaccinia virus reduced replication efficiency in nondividing cells both in vitro and in vivo ( 10). Viral ...
It is a member of the poxvirus family, the largest & most complex of the vertebr- ate viruses (230x300 nanometres in size). ... False-colour transmission electron micrograph of vaccinia virus. ... Replication of the DNA & the formation of the viral progeny ... The vaccinia virus causes cowpox, a disease of cattle & humans that causes skin lesions resembling those of smallpox, but ... False-colour transmission electron micrograph of vaccinia virus. It is a member of the poxvirus family, the largest & most ...
... innate immune responses in restricting vaccinia viral replication (7).. Two major classes of antimicrobial peptides are ... also inhibits virus replication, particularly enveloped viruses, including HSV1, HSV2, CMV, vesicular stomatitis virus, and ... Many of these adverse events may relate to a failure of the host to control vaccinia virus replication and dissemination. ... Dermal infection with vaccinia virus reveals roles for virus proteins not seen using other inoculation routes. J. Gen. Virol. ...
The Vaccinia virus (VACV) effector protein E3 is required for viral replication and pathogenesis; however not all of its ... Various pattern recognition receptors (PRRs) sense viral infections and stimulate pathways that promote the expression of genes ... a well-characterized sensor of viral nucleic acids in dendritic cells. Knockdown of DHX9 in the monocytic cell line phenocopied ... required for an antiviral immune response, such as those encoding interferons and interleukin-6 (IL-6). Many viruses encode ...
"Vaccinia virus G1 protein: absence of autocatalytic self-processing, Archives of Virology" on DeepDyve, the largest online ... The vaccinia virus G1L putative metalloproteinase is essential for viral replication in vivo ... Vaccinia virus G1 protein: absence of autocatalytic self-processing. Vaccinia virus G1 protein: absence of autocatalytic self- ... the PI3K/Akt pathway early during vaccinia and cowpox virus infections is required for both host survival and viral replication ...
Modified vaccinia virus Ankara delivery into the tumor in addition to systemic delivery of an immune checkpoint inhibitor ... It is not known whether viral replication is necessary for the antitumor effects of the DNA virus when delivered intratumorally ... "We were pleasantly surprised that inactivated oncolytic vaccinia virus works better than live virus," noted Deng. "These ... Inactivated Vaccinia Virus Safe and Effective Against Advanced Cancers Alone or in Combination with Immune Checkpoint ...
In addition, pre-treatment of Vero cells with ATA for up to 72 h also resulted in effective suppression of ZIKV replication ... In this study, we evaluated ATA as a potential antiviral drug against ZIKV replication. The antiviral activity of ATA against ... In this study, we evaluated ATA as a potential antiviral drug against ZIKV replication. The antiviral activity of ATA against ... Overall, these results demonstrate that ATA has potent inhibitory activity against ZIKV replication and may be considered as a ...
The high-resolution structure that has been obtained of components of the vaccinia virus DNA replication machinery will ... This protein is essential for the replication of the viral genome. The structure allows an understanding of anti-viral ... The vaccinia virus DNA polymerase structure provides insights into the mode of processivity factor binding, N. Tarbouriech (a ... Figure 2. (Left panel) Model of the vaccinia virus DNA polymerase in elongation mode with bound template strand (blue), the ...
Replication of vaccinia virus can be enhanced among persons with immunodeficiency diseases and among those with ... progressive vaccinia, severe generalized vaccinia, and severe ocular viral implantation) (Table 2). ... and other viruses (27--32). Recombinant vaccinia viruses have been created from different strains of vaccinia virus. In the ... vaccinia virus, recombinant vaccinia viruses derived from nonhighly attenuated vaccinia strains, or other Orthopoxviruses that ...
It appeared to Kempe, that the presence of the antibodies blocked viral replication and therefore a transfusion of antibodies ... Vaccinia virus Eczema vaccinatum Gamma globulin Smallpox Vaccine: Contraindications, Administration, and Adverse Reactions CDC ... Humoral and cell-mediated immune responses in humans before and after revaccination with vaccinia virus. Infect Immun. 1978;19: ... Vaccinia immune globulin (VIG) is made from the pooled blood of individuals who have been inoculated with the smallpox vaccine ...
Previous studies demonstrated that gene A55R encodes a protein that is nonessential for VACV replication yet affects viral ... Vaccinia virus gene A36R encodes a Mr 43-50 K protein on the surface of extracellular enveloped virus. Virology 204:376-390. ... Dermal infection with vaccinia virus reveals roles for virus proteins not seen using other inoculation routes. J Gen Virol 83: ... Virus-Cell Interactions. Vaccinia Virus BBK E3 Ligase Adaptor A55 Targets Importin-Dependent NF-κB Activation and Inhibits CD8+ ...
"Vaccinia virus DNA ligase recruits cellular topoisomerase II to sites RT of viral replication and assembly."; RL J. Virol. 82: ... Vaccinia virus (strain Western Reserve) (VACV) (Vaccinia virus (strain OS WR)). OC Viruses; dsDNA viruses, no RNA stage; ... RX PubMed=2587253; DOI=10.1093/nar/17.22.9039; RA Kerr S.M., Smith G.L.; RT "Vaccinia virus encodes a polypeptide with DNA ... Recruits CC cellular topoisomerase II to sites of viral replication and CC assembly. CC -!- CATALYTIC ACTIVITY: ATP + ( ...
Zou W et al. Degradation of Herpes Simplex Virus-1 Viral miRNA H11 by Vaccinia Virus Protein VP55 Attenuates Viral Replication. ... Microbiology Organism Virus DNA Virus double stranded DNA Virus Herpes simplex Share by email ... Shen MX et al. Antiviral Properties of R. tanguticum Nanoparticles on Herpes Simplex Virus Type I In Vitro and In Vivo. Front ... This IE protein is a multifunctional protein capable of migrating to the nucleus, binding to DNA, trans-activating other viral ...
The resulting recombinant vaccinia plasmids were again sequenced and used for the construction of recombinant vaccinia viruses ... 1990) The replication of viral and cellular DNA in human herpesvirus 6-infected cells. Virology 175:199-210. ... p7.5K131 vaccinia virus plasmid under the control of the p7.5K promoter and were used to generate recombinant vaccinia viruses ... recombinant vaccinia virus. CBLC. cord blood lymphocyte. EGFP. enhanced green fluorescent protein. CDV. cidofovir. GCV. ...
Additional viral proteins are needed to maintain adequate levels of deoxyribonucleotides for DNA replication, including a ... Construction of an Array of Vaccinia Virus Proteins.. Our strategy was to test each pairwise combination of vaccinia virus ORFs ... Preparation of Viral DNA.. Vaccinia virus was purified by sucrose gradient sedimentation, and DNA was extracted as described ( ... Each vaccinia virus ORF was amplified from viral genomic DNA in HotStart50 tubes (Life Technologies) essentially as described ...
Expression of the viral marker gene ruc-gfp facilitated real-time monitoring of infection and replication. Furthermore in ... Oncolytic virotherapy using replication-competent vaccinia virus (VACV) is a promising new strategy to treat human cancers. The ... Recombinant vaccinia virus GLV-1h68 is a promising oncolytic vector in the treatment of cholangiocarcinoma. ...
First, we demonstrate that vaccinia virus uniquely requires VRK2 for viral repli- cation in the absence of B1, unlike other DNA ... Employing execution point analysis, we reveal that virus replication proceeds normally through early protein translation and ... The vaccinia virus B1 protein kinase is involved in promoting multiple facets of the virus life cycle and is a homolog of three ... Employing loss-of-function analy- sis, we demonstrate that vaccinia viruss dependence on VRK2 is only observed in the presence ...
Viral replication is blocked at a late stage of virion assembly, so, importantly, viral and recombinant protein synthesis is ... MVA is a highly attenuated strain of vaccinia virus that is unable to replicate efficiently in human cell lines and most ... Replication-deficient recombinant MVA has been seen as an exceptionally safe viral vector. This safety in man is consistent ... RNA Virus Infections. Virus Diseases. Respiratory Tract Infections. Respiratory Tract Diseases. Vaccines. Immunologic Factors. ...
For another DNA virus, vaccinia virus, B1, one of the two viral protein kinases, is required for viral DNA replication (45). ... 1990) Temperature-sensitive vaccinia virus mutants identify a gene with an essential role in viral replication. J. Virol. 64: ... Studying viral protein kinases might therefore lead to an understanding of the mechanisms of virus replication and virus-cell ... REPLICATION. A Protein Kinase Activity Associated with Epstein-Barr Virus BGLF4 Phosphorylates the Viral Early Antigen EA-D In ...
Unlike the pilot study where neutralizing titers were not detected until after virus challenge, modest neutralizing titers were ... Lassa virus (LASV) causes a severe, often fatal, hemorrhagic fever endemic to West Africa. Presently, there are no FDA-licensed ... Replication competent viral-vectored candidate vaccines include recombinant vaccinia virus [11], recombinant vesicular ... Early and strong immune responses are associated with control of viral replication and recovery in lassa virus-infected ...
... and that Vaccinia virus, the prototypic member of the pox family, persists as a mainstay of vaccine design and has potential as ... occurs through receptors seemingly geared directly at viral products and that NK cells can provide a memory response to viral ... and that Vaccinia virus, the prototypic member of the pox family, persists as a mainstay of vaccine design and has potential as ... Not only do we realize viruses have many immune evasion strategies to escape NK cell responses, but that stimulation of NK cell ...
  • Synthesis of biologically active influenza virus core proteins using a vaccinia virus-T7 RNA polymerase expression system. (
  • An in vivo system in which expression of a synthetic influenza virus-like chloramphenicol acetyltransferase (CAT) RNA is driven by influenza virus proteins synthesized from cloned cDNAs has been developed. (
  • Determination of influenza virus proteins required for genome replication. (
  • In vitro reconstitution of active influenza virus ribonucleoprotein complexes using viral proteins purified from infected cells. (
  • A vaccinia virus lacking A10L: viral core proteins accumulate on structures derived from the endoplasmic reticulum. (
  • Viruses have evolved a number of mechanisms, encoding a large number of specific proteins, designed to interfere with host antiviral defense to maximize viral replication ( 11 , 12 ). (
  • Skern, T. 2017-05-18 00:00:00 Vaccinia virus relies on a series of proteolytic cleavage events involving two viral proteins, I7 and G1, to complete its life cycle. (
  • Many viruses encode effector proteins that subvert this response by targeting host proteins involved in PRR signaling pathways. (
  • Vaccinia virus (VACV) evades the host immune response by expressing scores of immunomodulatory proteins. (
  • The identification of host and virus proteins that modulate the induction of immunological memory is important for improving virus-based vaccine design and efficacy. (
  • In viruses, the expression of BTB-BACK Kelch-like (BBK) proteins is restricted to poxviruses and conserved within them, indicating the importance of these proteins for these medically important viruses. (
  • To detect interactions between proteins of vaccinia virus, we carried out a comprehensive two-hybrid analysis to assay every pairwise combination. (
  • We constructed an array of yeast transformants that contained each of the 266 predicted viral ORFs as Gal4 activation domain hybrid proteins. (
  • In the majority of cases, however, one of the interacting proteins was known to be involved in DNA replication, transcription, virion structure, or host evasion, thereby providing a clue to the role of the other uncharacterized protein in a specific process. (
  • Vaccinia virus has a genome of approximately 190 kbp and can potentially express more than 200 proteins, allowing an exceptional degree of independence from the host ( 3 ). (
  • Virus-encoded proteins involved in transcription include a multicomponent DNA-dependent RNA polymerase, an assortment of transcription factors, and enzymes that cap, methylate, and polyadenylylate mRNA ( 4 ). (
  • Of the eight virus-encoded proteins that have been implicated in DNA replication, four are directly involved in DNA polymerization, and others (such as a type I DNA topoisomerase, a single-stranded DNA-binding protein, a DNA ligase, and a DNA-RNA helicase) have other roles ( 5 ). (
  • Additional viral proteins are needed to maintain adequate levels of deoxyribonucleotides for DNA replication, including a thymidine kinase, a thymidylate kinase, a deoxyribonucleotide reductase, and a deoxyuridine triphosphatase. (
  • At least 30 proteins form the core and membrane components of virus particles ( 6 , 7 ). (
  • Other viral proteins interact with host components to facilitate virus dissemination, prevent apoptosis, and attenuate immune responses ( 8 , 9 ). (
  • Each of the ≈70,000 potential pairwise combinations of proteins was assayed, identifying putative interactions among both characterized viral proteins and those of unknown function. (
  • Antibodies against the external proteins of influenza can prevent the virus from infecting cells and either prevent infection or limit the spread of infection. (
  • Several APOBEC3 proteins, particularly APOBEC3D, APOBEC3F, and APOBEC3G, induce G-to-A hypermutations in HIV-1 genome, and abrogate viral replication in experimental systems, but their relative contributions to controlling viral replication and viral genetic variation in vivo have not been elucidated. (
  • This physical autonomy from the host nucleus suggests that poxvirus genomes encode the full repertoire of proteins committed for genome replication. (
  • The loss of H5 does not compromise the accumulation of other early viral replication proteins or the uncoating of the virion core, suggesting that H5 plays a direct and essential role in facilitating DNA synthesis. (
  • Poxviruses must establish cytoplasmic niches that support replication, and the genomes must encode the repertoire of proteins necessary for genome synthesis. (
  • However, the mode of the initial recruitment of SET proteins to target genes and the way that their association with the genes is maintained after replication are not known. (
  • The binding of single-stranded nucleic acids might play a role in the initial recruitment of the proteins to target genes, in the maintenance of their association after DNA replication, or in sustaining DNA stretches in a single-stranded configuration to allow for continuous transcription. (
  • Holowczak 1983) and focus on viral proteins whose participation in DNA replication is presumed on the basis of genetic or biochemical data. (
  • The plasmid encoding the antigenome sequence was transfected into cells previously infected with recombinant vaccinia virus that expressed T7 RNA polymerase, together with helper plasmids that expressed the viral replication proteins, NP, P, and L, under the control of the T7 polymerase promoter. (
  • Rather the amino acid is necessary for the expression of the late viral functions such as synthesis of viral coat proteins and production of complete infectious virions. (
  • Arginine is involved in the synthesis of viral proteins and it has been hypothesised that arginine is necessary for the formation of a functional protein that is essential for virion maturation. (
  • 1) We will continue to characterize BAF's impact on vaccinia DNA replication as well as examine how this poxvirus deals with other known DNA sensor proteins. (
  • Orthopoxviruses (OPXV) encode many proteins that are not essential for viral replication , but are resp. (
  • This research expands our understanding of the role of host proteins in viral replication and the innate immune response to HIV infection, and can be extended to DNA viruses such as HSV and vaccinia," added Guo. (
  • The early genes, which account for approximately half of the genome and are transcribed prior to DNA replication, encode many of the proteins involved in viral DNA replication and intermediate gene expression. (
  • The intermediate genes, of which only a handful have been identified, are expressed after the onset of DNA replication, and encode proteins that are activators of late gene expression. (
  • The late genes encode many proteins required for the transcription of early genes, the viral structural proteins and the enzymes necessary to process these proteins into their mature form. (
  • RNA viruses and retroviruses commonly undergo formative proteolysis in which large polyproteins are cleaved by viral encoded proteinases to produce the structural and nonstructural proteins required for morphogenesis. (
  • DNA viruses such as poxviruses and adenoviruses commonly use another type of proteolysis, called morphogenic proteolysis where precursor proteins are first synthesized and then cleaved by viral proteinases to produce the mature form of the protein. (
  • These viral proteins are present in smallpox, monkey pox and many other poxes, and they are very homologous," she said. (
  • It was also shown that the ionic strength, ionic species, and serum proteins present in the medium significantly altered the adsorption kinetics of the virus. (
  • These processes are associated with the production of antigenic proteins that make the virus vulnerable to immune control mechanisms 'warning' the host of the presence of an invader [ 1 ]. (
  • There are two classes of viral immunoregulatory proteins: the proteins encoded by genes having sequence similarity with cellular genes and those coded by genes without any sequence similarity to cellular genes. (
  • All these proteins are responsible for recognizing viral components and induce proinflammatory cytokine expression or interferon (IFN) response factors. (
  • Viruses encode homologs of complement regulatory proteins that are secreted and block complement activation and neutralization of virus particles. (
  • Spanning the viral membrane are three proteins: hemagglutinin (HA), neuraminidase (NA), and M2. (
  • After the synthesis of new copies of viral proteins and genes, these components assemble into progeny virus particles, which then exit the cell (reviewed by Roizman and Palese, 1996). (
  • Different viral proteins play a role in each of these steps. (
  • In addition, animal virus genomes contain elements and encode proteins that are very useful for the design of vectors for gene cloning and expression in mammalian cells. (
  • Poxviruses are DNA viruses that express numerous proteins to subvert the host immune response. (
  • The engagement of such RNA receptors leads to the rapid transcription of genes encoding anti-viral proteins via the activation of transcription factors belonging to the interferon regulatory factor (IRF) and nuclear factor-kappa B (NF-κB) families. (
  • Recombinant HIV protein including HIV envelopes, envelope derivatives, Virus Like Particles, as well as formulations of HIV proteins with immune enhancers such as adjuvants and immune modulators. (
  • Here, we have fully characterized the primary CTL response to autologous virus Env, Gag, and Tat proteins in three patients, and investigated the extent, kinetics, and mechanisms of viral escape from epitope-specific components of the response. (
  • To begin to address these questions, we analyzed the epitope specificity, breadth, and pattern of immunodominance within the primary CTL response to autologous virus Env, Gag, and Tat proteins in addition to the extent, kinetics, and pathways of virus escape during acute and early HIV-1 infection in three patients representative of groups establishing persisting viral loads in the highest and lowest ranges ( 10 ). (
  • The viroplasm is where components such as replicase enzymes, virus genetic material, and host proteins required for replication concentrate, and thereby increase the efficiency of replication. (
  • Disruption of cellular membranes can, for example, slow the transport of immunomodulatory proteins to the surface of infected cells and protect against innate and acquired immune responses, and rearrangements to cytoskeleton can facilitate virus release. (
  • It is possible that a cellular response originally designed to reduce the toxicity of misfolded proteins is exploited by cytoplasmic viruses to improve their replication, the virus capsid synthesis, and assembly. (
  • On the other hand, MVA retains the E3L gene encoding a bifunctional Z-DNA/dsRNA binding protein, a key vaccinia virulence factor [27] - [35] . (
  • lmmunolocalization experiments have shown the putative R2 binding protein to be localized at the sites of viral DNA synthesis. (
  • Our research further characterized the role of B1 during vaccinia infection to gain novel insights into its regulation and integration with cellular signaling pathways. (
  • Together, our studies of B1 and B12 present novel evidence that a paralogous kinase-pseudokinase pair can exhibit a unique epistatic relationship in a virus, and orchestrate yet-to-be-discovered nuclear events during infection. (
  • We reported previously that wild-type vaccinia (WT VAC) infection of epidermal cDCs fails to induce the production of type I IFN and attenuates innate immune responses to lipopolysaccharide (LPS) or poly(I∶C) [16] . (
  • Infection of human or murine pDCs with live WT VAC also fails to induce type I IFN production, whereas infection with heat-inactivated vaccinia (Heat-VAC, by incubating at 55°C for 1 h) induces TLR7/MyD88-dependent type I IFN production [17] , [18] . (
  • Vaccinia N1 is a 14-kDa cytosolic protein that contributes to virulence in murine infection models [25] , [26] . (
  • Inoculation with vaccina virus produces a localized skin infection. (
  • 3 This finding may contribute to infection with bacteria and selected viruses, including herpesviridae (HSV, varicella-zoster virus) and vaccinia virus. (
  • Resolution of infection and protection against reinfection with viruses depend on cooperation between innate and adaptive immune processes. (
  • The VGF gene encodes the vaccinia growth factor, a secreted protein produced early in viral infection that acts as a mitogen to prime surrounding cells for subsequent viral infection. (
  • Furthermore, G1 itself is cleaved during vaccinia virus infection. (
  • Deletion of SPI-2 leads to virus attenuation in vivo (observed in mice model after intranasal infection) but without any remarkable influence on the host immune response. (
  • These infectious agents are generally handled in infection-controlled rooms, and adverse events have been reported in patients when the viruses are administered at high doses or if the patients are immune-compromised. (
  • Viral infection of cells is sensed by pathogen recognition receptors that trigger an antiviral innate immune response, and consequently viruses have evolved countermeasures. (
  • Intradermal infection of mice with a virus lacking A55R (vΔA55) increased VACV-specific CD8 + T-cell proliferation, activation, and cytotoxicity in comparison to levels of the wild-type (WT) virus. (
  • HHV-6 infection in the majority of cases results from the reactivation of latent virus during immunosuppression, as in transplant recipients and in persons infected with HIV. (
  • Expression of the viral marker gene ruc-gfp facilitated real-time monitoring of infection and replication. (
  • Once a cell has been infected with the virus, it is then vulnerable to T cell attack resulting in the destruction of infected cells so that no more virus can be produced and the infection is controlled. (
  • Seasonal influenza infection results in a T cell response to the virus which can protect against subsequent infection. (
  • To further investigate Toll-like receptor signaling in vaccinia infection, we first focused on TRIF, the only known adapter protein for TLR3. (
  • Unexpectedly, bioluminescence imaging showed that mice lacking TRIF are more susceptible to vaccinia infection than wild-type mice. (
  • Following respiratory infection with vaccinia, mice lacking TLR4 signaling had greater viral replication, hypothermia, and mortality than control animals. (
  • We recently reported that Toll-like receptor 3 (TLR3), which recognizes double-stranded RNA, acts in vaccinia infection in a way that is detrimental to the host. (
  • In this paper, we report that mice lacking TRIF are more susceptible to vaccinia infection than wild-type controls. (
  • We report our findings that TLR4 has a protective effect in vaccinia infection. (
  • Mice with a nonfunctional mutant version of TLR4 are more susceptible to vaccinia infection than wild-type controls. (
  • Rather, TLR4 recognizes a molecule in or on vaccinia virus to bring about a protective response that may be due to an ability to diminish the degree of inflammation caused by vaccinia infection. (
  • Nevertheless, potential bioterrorist release of Variola major , the causative agent for smallpox, and human infection with monkeypox or other zoonotic orthopoxviruses has heightened interest in this family of viruses [2] . (
  • In recent years, our understanding of the role of natural killer (NK) cells in the response to viral infection has grown rapidly. (
  • This review focuses on recent advances in understanding the role of NK cells in the immune response to poxviruses, the receptors involved in activation of NK cells during poxvirus infection, and the viral evasion strategies poxviruses employ to avoid the NK response. (
  • NK cells can limit viral replication directly by lysing virus-infected cells, and are also stimulated during a viral infection through cytokines to produce antiviral cytokines such as interferon-gamma (IFN-γ). (
  • While the role of NK cells during herpes virus infection has been well established and dissected, poxviruses also present an interesting family of viruses to consider in the context of the NK cell response. (
  • The primary focus of Pant's research is to understand how vaccinia virus infection repurposes the nutrient resources of host cells to support optimal viral replication. (
  • Here we show that cultured primary human placental trophoblasts are highly resistant to infection by a number of viruses and, importantly, confer this resistance to nonplacental recipient cells by exosome-mediated delivery of specific microRNAs (miRNAs). (
  • Viral biodistribution was determined in nude mice bearing PANC-1 xenografts, and infection in tumors confirmed histologically and optically via Green Fluorescent Protein (GFP) and bioluminescence. (
  • However, for sufferers of atopic dermatitis, vaccination itself poses a problem because these individuals are prone to developing the condition eczema vaccinatum: an exacerbated skin infection that follows inoculation with the vaccinia virus used in smallpox vaccination. (
  • Corticosteroids may accelerate spread of viral infection. (
  • 2) We will explore the question of whether BAF is capable of responding to other sources of foreign DNA including plasmids or during infection with other viruses. (
  • Jamin A, Thunuguntla P, Wicklund A, Jones C, Wiebe MS . Barrier to auto integration factor becomes dephosphorylated during HSV-1 Infection and Can Act as a host defense by impairing viral DNA replication and gene expression. (
  • Conversely, epithelial cells with no detectable NO synthesis restricted viral replication when transfected with a complementary DNA encoding inducible NO synthase or treated with organic compounds that generate NO. In mice, an inhibitor of NO synthase converted resolving ectromelia virus infection into fulminant mousepox. (
  • Importantly, we were able to show that deficiencies in NLRX1 reduce HIV replication , suggesting that the development of small molecules to modulate the innate immune response may inhibit viral transmission and promote immunity to infection," said Chanda. (
  • Patients with progressive vaccinia (PV) have been given the smallpox vaccination (or have been exposed to a vaccinee) and have significant underlying immunocompromise (eg, HIV, underlying malignancy, transplant recipient) preventing them from controlling and eradicating the vaccinia infection. (
  • There are two essential components to the development of progressive vaccinia: (1) exposure to the smallpox vaccination (which contains live vaccinia virus) and (2) significant systemic immunocompromise (eg, HIV infection, chemotherapy recipients). (
  • Failure to mount sufficient humoral and cellular responses to vaccinia virus results in slow, progressive enlargement of a local vaccinia infection (smallpox vaccination site), which requires improvement of host immune function and antivirals/biologics for cure. (
  • One recently described monoclonal antibody (E106) protects mice against infection of DENV-1 when administered before or several days after virus infection. (
  • Dengue virus (DENV) infection in humans causes symptoms ranging from a mild febrile illness to a severe and sometimes fatal disease. (
  • Estimates suggest that greater than 90% of severe cases occur during secondary infection with a heterologous DENV serotype, possibly because sub-neutralizing amounts of cross-reactive antibody facilitate viral entry into myeloid cells expressing Fc-γ receptors, a phenomenon termed antibody-dependent enhancement of infection (ADE) [6] . (
  • Antibody-mediated protection against homologous DENV infection correlates with a neutralizing antibody response directed predominantly against the viral E protein [7] . (
  • Introduction Respiratory syncytial virus (RSV) infection causes respiratory disease throughout life, with infants and the elderly at risk of severe disease and death. (
  • Here, we combine these two platforms to evaluate the efficacy of a viral vectored vaccination regimen in protecting ferrets from H3N2 influenza virus infection. (
  • Decades of HIV/AIDS research suggest increasingly that the body must mount a powerful attack against infection by the virus early if this innate immune response is to halt the viral invasion in its tracks, understanding the underlying processes might allow researchers to improve the effectiveness of vaccines. (
  • Loss of A43R expression had no discernible effect on plaque size or virus replication in cell culture and little effect on virulence in a mouse intranasal infection model. (
  • To further investigate Toll-like receptor signaling in vaccinia infection, we first focused on TRIF, the only known adapter protein for TLR3.We then focused on TLR4, the other Toll-like receptor that signals through TRIF.The mechanism of TLR4-mediated protection was not due to increased release of proinflammatory cytokines or changes in total numbers of immune cells recruited to the lung. (
  • TRIF−/− mice are more susceptible to vaccinia infection than WT.TRIF−/− and WT BL/6 mice were infected with 1×104 pfu Vac-FL. (
  • Unexpectedly, susceptibility of TRIF−/− mice to vaccinia infection was distinct from that of the TLR3−/− mice. (
  • Chronic hepatitis C virus (HCV) infection is a leading cause of chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma [ 1 - 3 ]. (
  • In this study, we analysed the specific modulation of the host cell's gene expression profile by cowpox, monkeypox and vaccinia virus infection. (
  • We aimed to identify mechanisms that are either common to orthopoxvirus infection or specific to certain orthopoxvirus species, allowing a more detailed description of differences in virus-host cell interactions between individual orthopoxviruses. (
  • To this end, we analysed changes in host cell gene expression of HeLa cells in response to infection with cowpox, monkeypox and vaccinia virus, using whole-genome gene expression microarrays, and compared these to each other and to non-infected cells. (
  • Most noticeable was an induction of genes involved in leukocyte migration and activation in cowpox and monkeypox virus-infected cells, which was not observed following vaccinia virus infection. (
  • The influence of various culture parameters on infection and replication of recombinant vaccinia virus in HeLa cells was examined during various phases of viral replication. (
  • The lysosomotropic base chloroquine was found to enhance viral infection more than 2-fold during the penetration step of viral infection. (
  • Finally, it was demonstrated that viral infection of HeLa cells grown in 4-L bioreactor batch cultures resulted in increased death and glucose uptake rates and significantly lower growth rates. (
  • The cowpox virus (CPV) complement inhibitor, termed inflammation modulatory protein (IMP), blocks immunopathological tissue damage at the site of infection, presumably by inhibiting production of the macrophage chemo attractant factors C3a and C5a. (
  • Viruses, being obligatory parasites of their host cells, rely on a vast supply of cellular components for their replication, regardless of whether infection leads to cell death or to the state of persistence. (
  • Can bind to viral RNAs and via association with MAVS/IPS1 and DDX58/RIG-I is thought to induce signaling in early stages of infection. (
  • During virus infection detection of nucleic acids is crucial for the inflammatory response. (
  • Both cells and mice lacking DNA-PKcs show attenuated cytokine responses to both DNA and DNA viruses but not to RNA or RNA virus infection. (
  • have found that it is also present at high levels within fibroblasts, cells that are often primary targets of viral infection, and they go on to explain how the detection of DNA by DNA-PK triggers a sequence of events that leads to the innate immune response being activated. (
  • These events include the transcription of type I interferon, chemokines and cytokines in a manner that depends on the presence IRF-3, a transcription factor that has a central role in the response of the immune system to viral infection. (
  • In contrast, nude mice that received T cells and 7 day treatment with ST-246 survived infection and exhibited reduced viral loads compared with non-reconstituted and ST-246-treated mice after ST-246 was stopped. (
  • Robust VV-specific CD4 T-cell responses during primary infection are likely essential to controlling VV replication. (
  • Although there is increasing interest in cytolytic CD4 T-cells across many viral infections, the importance of these cells during acute VV infection is unclear. (
  • In this paper, a general viral infection model with humoral immunity is investigated. (
  • The theoretical results and corresponding numerical simulations show that the intracellular latency, both of virus-to-cell infection and cell-to-cell infection have direct effects on the global dynamics of the general viral infection model. (
  • CD8 + cytotoxic T lymphocytes (CTLs) play an important role in containment of virus replication in primary human immunodeficiency virus (HIV) infection. (
  • In all three individuals, we observed variation beginning within weeks of infection at epitope-containing sites in the viral quasispecies, which conferred escape by mechanisms including altered peptide presentation/recognition and altered antigen processing. (
  • HIV-1-specific CD8 + CTL responses are induced in primary infection ( 1 , 2 ) and multiple lines of evidence suggest that they make an important contribution to control of acute and early viral replication (for review see reference 3 ). (
  • however, problems associated with studying T cell responses in natural acute HIV-1 infection, including limited availability of suitable samples and the sequence variability among infecting virus strains, have made it difficult to generalize these findings, leaving many important questions unanswered. (
  • CTL escape has been shown to be a hallmark of acute/early simian immunodeficiency virus infection ( 9 ). (
  • In this way, it will be possible to dissect out the immune responses to replication-competent viruses and to tumors undergoing oncolytic infection. (
  • The murine cytomegalovirus (MCMV) immediate early gene 1 (IE1) encodes a nonstructural 89-kDa phosphoprotein (pp89) which is essential for viral replication and plays a key role in generation of protective CD8+ cytotoxic T lymphocytes (CTLs) during natural infection. (
  • The number and the size of viroplasms depend on the virus, the virus isolate, hosts species, and the stage of the infection. (
  • in many cases, the cellular rearrangements caused during virus infection lead to the construction of sophisticated inclusions -viroplasms- in the cell where the factory will be assembled. (
  • Mass spectrometry analysis of VACV-infected mouse embryonic fibroblasts showed that E3 bound to DExD/H-box helicase 9 (DHX9), a well-characterized sensor of viral nucleic acids in dendritic cells. (
  • Previous studies demonstrated that gene A55R encodes a protein that is nonessential for VACV replication yet affects viral virulence in vivo . (
  • Furthermore, immunization with vΔA55 induced increased protection to intranasal VACV challenge compared to the level with control viruses. (
  • Using vaccinia virus (VACV), the smallpox vaccine, we report that the VACV BBK protein A55 dysregulates NF-κB signaling by disrupting the p65-importin interaction, thus preventing NF-κB translocation and blocking NF-κB-dependent gene transcription. (
  • Oncolytic virotherapy using replication-competent vaccinia virus (VACV) is a promising new strategy to treat human cancers. (
  • The Vaccinia Virus (VACV) B1 and Cellular VRK2 Kinases Promote VACV Re" by Annabel T. Olson, Zhigang Wang et al. (
  • We have taken a number of approaches to improve the safety and efficacy of recombinant vaccines for use in humans and animals, including: choice of the strain of vaccinia virus (VACV) used as a vector, insertional inactivation of virulence and immunoregulatory genes of VACV, and expression of cytokine genes that attenuate the vector by more than a million-fold without reduction in immunogenicity. (
  • These strategies are illustrated by providing examples of recombinant VACV (rVACV) vaccines we have developed for rinderpest, vesicular stomatitis, simian immunodeficiency virus, and smallpox. (
  • The traditional smallpox vaccine is a live vaccinia virus (VACV) responsible for rare, but serious post-vaccinal encephalitis (PVE). (
  • Moreover, VACV was titrated in blood, spleen and brain after intra-cardiac perfusion to detect viral replication and brain invasion. (
  • Hepatitis B virus (HBV) polymerase and possibly vaccinia virus (VACV) protein K7 inhibit IFN-beta induction probably by dissociating DDX3X from TBK1 or IKBKE. (
  • Whole body bioimaging was used to study dissemination of vaccinia virus (VACV) in normal and in immune deficient (nu-/nu-) mice protected from lethality by post challenge administration of ST-246. (
  • Interferon-γ (IFN-γ) is an attenuating factor for vaccinia virus (VACV), decreasing its virulence in vivo by more than a million fold. (
  • The ability of cancer cells to evade apoptosis may permit survival of a recombinant vaccinia lacking antiapoptotic genes in cancer cells compared with normal cells. (
  • We conclude that this recombinant vaccinia vSP shows promise for oncolytic virus therapy. (
  • Recombinant vaccinia viruses (rVVs), expressing high levels of pU69 from two HHV-6 strains (representing the A and B variant), were constructed and used to compare the ganciclovir-phosphorylating capacity of pU69 and pUL97 in human cells. (
  • Buller RM, Smith GL, Cremer K, Notkins AL, Moss B (1985) Decreased virulence of recombinant vaccinia virus expression vectors is associated with a thymidine kinase-negative phenotype. (
  • Thus, the recombinant vaccinia virus LIVP-GFP is able to inhibit the growth of malignant cells with the MDR phenotype and tumour metastasis when administered in the early stages of tumour development. (
  • MVA has a 31-kb deletion of the parental vaccinia genome and was used successfully as a vaccine during the WHO-sponsored smallpox eradication campaign [4] - [6] . (
  • Certain military recruits continue to receive vaccinia vaccine owing to the concern for bioterrorism. (
  • In the United States, Dryvax became the first approved vaccinia virus vaccine in 1931. (
  • Vaccinia virus is the species now characterized as the constituent of smallpox vaccine. (
  • The effectiveness of vaccinia virus as a vaccine paramount was in this effort. (
  • The Wyeth vaccine strain of vaccinia virus was incubated with varying concentrations of human (LL-37) and murine (CRAMP) cathelicidins, human α-defensin (HBD-1, HBD-2), and a control peptide. (
  • Host reaction was comparable to that on MVA virus (modified virus Ankara) which serves as a smallpox vaccine nowadays. (
  • Vaccinia immune globulin (VIG) is made from the pooled blood of individuals who have been inoculated with the smallpox vaccine. (
  • In summary, this report describes the first target of a poxvirus-encoded BBK protein and a novel mechanism for DNA virus immune evasion, resulting in increased CD8 + T-cell memory and a more immunogenic vaccine. (
  • Vaccinia virus, the best-characterized member of this large family, was extensively used as the smallpox vaccine, has gained popularity as a mammalian expression vector, and is being tested as a recombinant vaccine against cancer and infectious diseases ( 2 ). (
  • In this report, we study the immune responses elicited in rhesus monkeys by a recombinant poxvirus vaccine and the degree of protection afforded against a pathogenic simian-human immunodeficiency virus SHIV-89.6P challenge. (
  • A safe and effective human immunodeficiency virus type 1 (HIV-1) vaccine is urgently needed to control the worldwide HIV-1 epidemic. (
  • It is therefore widely believed that HIV-1 vaccine candidates should elicit potent virus-specific CTL responses in addition to neutralizing antibody (NAb) responses. (
  • Other vaccine strategies capable of eliciting virus-specific CTL responses are therefore being evaluated. (
  • Safety concerns regarding vaccinia virus ( 31 ) have led to the development of a number of attenuated poxviruses as vaccine vectors, including NYVAC, fowlpox, canarypox, and modified vaccinia virus Ankara (MVA) ( 8 , 16 , 28 , 29 , 37 , 38 ). (
  • Vaccinia virus is the prototypic poxvirus, and it is used as both a model and a vaccine for the virus that causes smallpox. (
  • Immunization of rhesus monkeys with modified vaccinia Ankara (MVA) recombinants expressing the haemagglutinin-neuraminidase (HN) or fusion (F) glycoproteins of human parainfluenza virus type 3 (HPIV3) was compared with an intranasally-administered live, attenuated HPIV3 vaccine candidate, the cp45 derivative of the JS strain of wildtype HPIV3. (
  • The live, attenuated virus vaccine candidate induced almost complete resistance in both the upper and lower tracts. (
  • Given that human diseases caused by poxviruses can be as lethal as smallpox or as benign as Molluscum contagiosum, and that vaccinia virus, the prototypic member of the pox family, persists as a mainstay of vaccine design and has potential as an oncolytic virus for tumor therapy, further research in this area remains important. (
  • Vaccinia virus was used as the vaccine successfully to eradicate variola virus and remains under investigation as a general vaccine vector as well as an oncolytic virus. (
  • The Company's lead clinical-stage programs are: TG4010, a therapeutic vaccine against non-small cell lung cancer, Pexa-Vec, an oncolytic virus against liver cancer, and TG4001, a therapeutic vaccine against HPV-positive head and neck cancers. (
  • The Company has several other programs in clinical development, including TG1050 (a therapeutic vaccine for the treatment of chronic hepatitis B) and TG6002 (an oncolytic virus for the treatment of solid tumors). (
  • Vaccinia virus was used as a live vaccine to eradicate smallpox and is still used as a model to study infections caused by other members of the poxvirus family that cause significant morbidity and mortality in humans and economically important animals. (
  • His work has also identified key virus and host factors that interact at the interface of metabolism, which could lead to the development of novel strategies for the advancement of poxvirus-based tools for vaccine development and cancer treatment. (
  • Dhungel studies vaccinia virus, which is used as a live vaccine to eradicate smallpox. (
  • Vaccinia was given as a live vaccine against smallpox during the World Health Organization's successful campaign to eradicate smallpox 30 years ago. (
  • While vaccinia is no longer given as a routine vaccine, further study of this viral cousin of smallpox is warranted for at least two general reasons. (
  • Dengue virus (DENV) is a globally important mosquito-transmitted human pathogen for which there is no approved vaccine or antiviral therapy. (
  • RSV001 is a phase 1 (first-in-man), open-label, dose-escalation, clinical trial of novel genetic viral-vectored vaccine candidates PanAd3-RSV and modified vaccinia virus Ankara (MVA)-RSV. (
  • Because of this, there is an urgent need for a universal vaccine that induces broad protection against drifted seasonal and emerging pandemic influenza viruses. (
  • Overall, these results improve our understanding of vaccination platforms capable of harnessing both cellular and humoral immunity with the goal of developing a universal influenza virus vaccine. (
  • Vaccinia has also been widely used as a vehicle for vaccine delivery and has been shown to be highly effective in generating antigen-specific immune responses in DNA vaccine prime followed by vaccinia boost regimens ( 10 ). (
  • Through collaboration with the NIAID-funded HIV Vaccine Trials Network and Duke University NC, we have shown that targeting of selected vulnerable regions within the HIV proteome by CD8+ T cells is strongly associated with their capacity to inhibit HIV replication in vitro. (
  • We are planning a series of vaccine trials to evaluate vaccinations with HIV and/or HCV immunogens, each delivered by replication-defective chimpanzee adenovirus and MVA vectors, in healthy volunteers and in HIV-positive HCV-uninfected patients on ART. (
  • The present invention relates to novel adjuvants for vaccine compositions, and to compositions comprising at least one antigen, in particular an antigen of viral, bacterial or parasitic origin, and at least one adjuvant. (
  • ACAM2000, Smallpox (Vaccinia) Vaccine, Live, is a live vaccinia virus derived from plaque purification cloning from Dryvax® (Wyeth Laboratories, Marietta, PA, calf lymph vaccine, New York City Board of Health Strain) and grown in African Green Monkey kidney (Vero) cells and tested to be free of adventitious agents. (
  • These results have implications for HIV vaccine design, supporting the importance of restriction of viral escape from CD8 T cell control and suggesting means by which this may be achieved. (
  • With replicating viral vectors, levels of gene expression are higher and transduction efficiency is improved due to viral replication and subsequent spread to surrounding cells. (
  • Immunization with recombinant modified vaccinia virus Ankara (MVA) vectors expressing SIVmac239 gag-pol and HIV-1 89.6 env elicited potent Gag-specific CTL responses but no detectable SHIV-specific neutralizing antibody (NAb) responses. (
  • These results demonstrate that immune responses elicited by live recombinant vectors, although unable to provide sterilizing immunity, can control viremia and prevent disease progression following a highly pathogenic AIDS virus challenge. (
  • It remains to be determined whether other vaccination modalities, in particular live recombinant vectors, will provide a similar level of protection in monkeys challenged with the highly pathogenic virus SHIV-89.6P ( 32-34 ). (
  • With its proprietary Invir.IO TM , Transgene builds on its expertise in viral vectors engineering to design a new generation of multifunctional oncolytic viruses. (
  • One factor that has united the most successful oncolytic vectors has been the expression of an immune-activating transgene (GM-CSF), an indication that a key determinant of the activity of oncolytic viruses is their capacity to activate and target the immune response ( 9, 10 ). (
  • Expression of Hepatitis B virus S gene by herpes simplex virus type 1 vectors carrying .alpha. (
  • In a preferred embodiment of the invention, methods are provided for the production of viral vectors from large viral genomes (greater than 50 kbp) that incorporate nucleic acid insertions by direct in vitro ligation. (
  • In another preferred embodiment of this invention, viral vectors are provided from large viral genomes. (
  • These viral vectors accommodate nucleic acid inserts by direct in vitro ligation and facilitate the expression of foreign protein in eukaryotic cell systems. (
  • Furthermore, replication deficient viral vectors based on Chimpanzee Adenovirus Oxford 1 (ChAdOx1) and modified vaccinia Ankara (MVA) virus expressing the influenza virus internal antigens, the nucleoprotein (NP) and matrix 1 (M1) protein, can induce strong heterosubtypic influenza virus-specific T cell responses in vaccinated individuals. (
  • We utilized established viral vectors, the replication-deficient chimpanzee adenovirus serotype 63 (ChAd63), and the attenuated orthopoxvirus modified vaccinia virus Ankara (MVA), encoding RH5 from the 3D7 clone of P. falciparum. (
  • The vaccines comprise a conserved region immunogen, HIVconsv, delivered by replication-defective chimpanzee adenovirus and MVA vectors. (
  • We exploit the same potent viral vectors for delivery of a novel HPV immunogen that have proven safe and immunogenic for HIV and HCV. (
  • Viral vectors are viruses with new or modified genomes that remove the virus' pathogenicity. (
  • In order to be successful at transforming the defective genome, viral vectors must overcome physical barriers and immune responses. (
  • With the aid of more advanced models and a broader base of immunological knowledge, correction of genetic diseases currently untreatable may someday be achieved through the use of viral vectors. (
  • In time, viral vectors may be utilized as the main source of treatment for genetic diseases. (
  • The present invention also relates to infectious bovine rhinotracheitis-based viral vectors useful for the coexpression of foreign genes. (
  • Replication defective adenovirus vectors with low sero-prevalence and low T-cell reactivity in the relevant human populations. (
  • Replication competent viral vectors (e.g. (
  • Adeno-associated virus ( AAV) vectors for the delivery of broadly neutralizing antibodies. (
  • It is a member of the poxvirus family, the largest & most complex of the vertebr- ate viruses (230x300 nanometres in size). (
  • Cytoplasmic organization of POXvirus DNA replication. (
  • To increase our understanding of the poxvirus life cycle and to evaluate an approach that would be generally applicable to other large viruses, we initiated a genome-wide yeast two-hybrid analysis to identify vaccinia virus protein-protein interactions. (
  • These data support the hypothesis that H5 is a crucial participant in cytoplasmic poxvirus genome replication. (
  • DNA replication is arguably the most fundamental of biological processes and serves as a pivotal element in the poxvirus life cycle. (
  • Unraveling the mechanism of poxvirus replication and identifying the panoply of enzymatic activities which it requires has been a focus of much recent research. (
  • Vaccinia is a member of the poxvirus family, and is closely related to the smallpox and monkeypox viruses. (
  • JX594 is an oncolytic poxvirus derived from Wyeth strain vaccinia virus. (
  • Vaccinia poxvirus joins a herpesvirus and a host of other pathogens on a growing list of engineered viruses entering late-stage human testing against cancer. (
  • These data suggest that ST-246 protects immune competent mice from lethality and reduces viral dissemination in internal organs and poxvirus lesions. (
  • We have explored the deletion of two vaccinia virus host range/antiapoptosis genes, SPI-1 and SPI-2 , for their effects on the viral replication and their ability to induce cell death in infected normal and transformed cells in vitro . (
  • We have previously shown that a double deletion of the thymidine kinase ( TK ) and vaccinia growth factor ( VGF ) genes significantly decreases pathogenicity and increases tumor selectivity. (
  • These viruses contain approximately 200 genes in their genome. (
  • Various pattern recognition receptors (PRRs) sense viral infections and stimulate pathways that promote the expression of genes required for an antiviral immune response, such as those encoding interferons and interleukin-6 (IL-6). (
  • Although 10 years have passed since the genome of vaccinia virus was sequenced ( 3 ), the roles of about half of the genes remain entirely unknown. (
  • This IE protein is a multifunctional protein capable of migrating to the nucleus, binding to DNA, trans-activating other viral genes, and autoregulating its own synthesis. (
  • In a two-pronged attack, these viruses specifically target tumor cells while delivering a cargo of immune-boosting genes. (
  • Furthermore, the viruses can serve as a vehicle for delivering genes of interest to cancer cells. (
  • Recombinant viruses have been studied as vehicles of delivering genes of interest to cancer cells due to their transduction efficiency and potential oncolytic properties. (
  • In their research, Shisler and Xiao-Lu Jin, a research specialist in microbiology, found that a 5.2 kb segment of vaccinia virus DNA containing six genes was responsible for inhibiting a key cellular transcription factor called NF kappa B (NF-kB). (
  • NF-kB serves to turn on other host cell genes involved in anti-viral immune responses and inflammation. (
  • Understanding the molecular machinery involved may make it possible to eventually manufacture safer vaccines for smallpox and vaccinia-based vaccines for HIV by specifically manipulating genes, Shisler said. (
  • Viral-mediated gene therapy utilizes viral replication in order to correct mutations to genes in the human genome by inserting the corrected gene into the viral genome. (
  • A variety of hypoxia-selective and tumor-type-specific oncolytic adenoviruses, generated by incorporating hypoxia-responsive elements into synthetic promoters to control essential genes for viral replication or therapeutic genes, have been shown to be safe and efficacious. (
  • The life cycle of viruses generally involves attachment to cell surface receptors, entry into the cell and uncoating ofthe viral nucleic acid, followed by replication ofthe viral genes inside the cell. (
  • TY - JOUR T1 - Regulated expression of foreign genes in vaccinia virus under the control of bacteriophage T7 RNA polymerase and the Escherichia coli lac repressor. (
  • Finally, viruses have yielded invaluable reagents in molecular biology as, for example, the vaccinia virus vector for the expression of foreign genes. (
  • Since cytotoxic T lymphocytes (CTLs) are critical for controlling human immunodeficiency virus type 1 (HIV-1) replication in infected individuals, candidate HIV-1 vaccines should elicit virus-specific CTL responses. (
  • Live, attenuated virus vaccines have been shown to generate CTL and NAb responses capable of controlling a number of pathogenic viral challenges ( 10 , 40 , 41 ). (
  • This safety in man is consistent with the avirulence of MVA in animal models, where recombinant MVAs have also been shown to be protectively immunogenic as vaccines against viral diseases and cancer. (
  • These data establish that TLR4 mediates a protective innate immune response against vaccinia virus, which informs development of new vaccines and therapeutic agents targeted against poxviruses. (
  • Vaccinia virus is also used as an agent for cancer therapy and the development of vaccines against diseases such as HIV/AIDS, Ebola, influenza, MERS/SARS-coronavirus. (
  • Construction of live vaccines by using genetically engineered poxviruses: Biological activity of recombinant vaccina virus expressing influenza virus hemagglutinin," Proc. (
  • The findings, published today in Cell Host & Microbe, have important implications for improving HIV antiviral therapies , creating effective viral vaccines, and advance a new approach to treat cancer. (
  • Most Americans older than 40 received vaccinia as children in smallpox vaccines , but the company found no evidence that having had this vaccination hindered the effectiveness of the new virus. (
  • We observed that viral vectored vaccines expressing both stalk-targeting, chimeric HA constructs, and the NP+M1 fusion protein, in a prime-boost regimen resulted in the production of antibodies toward group 2 HAs, the HA stalk, NP and M1, as well as in induction of influenza virus-specific-IFNγ responses. (
  • We will also test next-generation viral vectored vaccines employing an HCV immunogen fused to HLA class II invariant chain. (
  • We are starting a new project to develop new multi-genotype vaccines for therapy of human papilloma virus (HPV) infections that are responsible for cervical cancer (0.5 million cases per year worldwide) and other anogenital cancers. (
  • The present invention relates to infectious bovine rhinotracheitis viruses which fail to produce any functional thymidine kinase as a result of an insertion in the thymidine kinase gene, vaccines against infectious bovine rhinotracheitis containing the same and methods for production and use of same. (
  • Understanding the role of CD4 CTL in the generation of an effective anti-viral memory may help develop more effective vaccines for diseases such as HIV. (
  • Some U.S. medical workers and military personnel have received vaccinations made of the live vaccinia virus, but while this tamer relative of smallpox normally doesn t cause disease, complications, including death, are possible especially among immune-compromised individuals. (
  • ACAM2000 is a live vaccinia virus that can be transmitted to persons who have close contact with the vaccinee and the risks in contacts are the same as those for the vaccinee. (
  • Furthermore, we show that vaccinia virulence factors E3 and N1 play inhibitory roles in the cytosolic DNA-sensing pathway. (
  • Thus, phosphorylation of vdUTPase appeared to regulate viral virulence and genome integrity by compensating for low cellular dUTPase activity in vivo. (
  • Vaccination with vaccinia virus has been directly responsible for the successful eradication of smallpox (variola). (
  • Laboratory personnel working with vaccinia and others for whom the benefits outweigh the risks of vaccination may also receive vaccinations. (
  • In 1796, when Jenner made his seminal report on vaccinia, the potential benefits of vaccination became widely accepted. (
  • It is used to treat individuals who have developed progressive vaccinia after smallpox vaccination. (
  • It appeared to Kempe, that the presence of the antibodies blocked viral replication and therefore a transfusion of antibodies from people who were immune due to vaccination, would help those in whom vaccination had failed. (
  • One of the great success stories of modern medicine is the eradication of smallpox virus that was declared in 1980 after a long vaccination campaign with vaccinia virus. (
  • We have also demonstrated that cytokine-augmented DNA vaccination elicited potent immune responses that effectively controlled viremia and prevented clinical disease progression following a pathogenic simian-human immunodeficiency virus SHIV-89.6P challenge ( 6 , 7 ). (
  • Although smallpox was declared eradicated by the World Health Organization in 1980, the threat of bioterrorism means that future vaccination against this virus is being considered. (
  • Progressive vaccinia (PV) represents the unchecked viral replication of vaccinia virus and expansion of a smallpox vaccination site in an immunocompromised host. (
  • The immune response induced by this vaccination regime ultimately reduced viral titers in the respiratory tract of influenza virus infected ferrets. (
  • A resulting trend in vector development for cancer therapy has been to explore replicating oncolytic viruses, such as adenovirus, herpes simplex virus, and vaccinia virus ( 1 - 5 ). (
  • It is active against herpes simplex and varicella zoster viruses, and has also been shown to inhibit vaccinia virus, cytomegalovirus and adenovirus. (
  • Arginine is required for the replication of human adenovirus type 2 (common cold) and is essential for the production of complete infectious virions. (
  • Certain viruses including HSV and adenovirus are characterised by their ability to cause latent (dormant) infections. (
  • ChAdOx1-HPV is a recombinant replication-incompetent chimpanzee-derived adenovirus (ChAdY25) viral vector. (
  • It reviews many of the replication-competent viruses currently being investigated for therapeutic use including herpes simplex virus, adenovirus, reovirus, parvovirus, vaccinia virus and Newcastle disease virus, and demonstrates how this approach is being translated to the clinic.Illustrating how virus-host interactions can be exploited for therapy, this book opens up new and promising perspectives for the treatment of cancer. (
  • These alterations are possible candidate mechanisms for the serious consequences of herpes viruses and vaccinia virus in this skin disease. (
  • Current oncolytic viruses including talimogene laherparepvec (T-VEC), an engineered herpes simplex virus that has been approved by the U.S. Food and Drug Administration for the treatment of advanced melanoma, are replication competent, said Deng. (
  • Tremendous knowledge has been gained in this area through the study of herpes viruses, but appreciation for the significance of NK cells in the response to other types of viral infections is growing. (
  • A mutation in herpes simplex virus 1 dUTPase (vdUTPase), which precluded its phosphorylation at Ser-187, decreased viral neurovirulence and increased mutation frequency in progeny virus genomes in the brains of mice where endogenous cellular dUTPase activity was relatively low, and overexpression of cellular dUTPase restored viral neurovirulence and mutation frequency altered by the mutation. (
  • Protective immunity against genital pathogens causing chronic infections, such as herpes simplex virus 2 (HSV-2) or human immunodeficiency virus, requires the induction of cell-mediated immune responses locally in the genital tract. (
  • Arginine bioavailability is absolutely necessary for the replication of herpes simplex virus, which causes cold sores/genital herpes. (
  • When arginine is not available, herpes viruses in cells are unable to complete a single replication cycle and cell damage is evident in infected cells. (
  • This antagonistic relationship might benefit people who suffer from frequent herpes outbreaks, such as cold sores or genital herpes, because arginine is needed by these viruses to reproduce. (
  • For example, Amgen talimogene laherparepvec (T-VEC) is a herpes simplex virus type 1 (HSV-1)-based OV that has been engineered to express granulocyte-macrophage colony-stimulating factor (GM-CSF), which may facilitate tumor clearance. (
  • Insertion of DNA sequences at a unique restriction enzyme site engineered for vector purposes into the genome of herpes simplex virus type 1, pp. 2931-2939. (
  • The ability of IFN-gamma to inhibit replication of ectromelia, vaccinia, and herpes simplex-1 viruses in mouse macrophages correlated with the cells' production of nitric oxide (NO). Viral replication was restored in IFN-gamma-treated macrophages exposed to inhibitors of NO synthase. (
  • In contrast, the human herpes simplex virus 8 encodes different analogs of IRF with negative dominant activity, allowing it to interfere with the activity of cellular IRFs [ 11 ]. (
  • The infected cell polypeptide 0 (ICP0) from Bovine herpes virus can interact with IRF3 and induce its proteasome-dependent degradation [ 12 ]. (
  • Replication of adenoviruses from both groups B and C is inhibited, yet replication of herpes simplex virus is enhanced. (
  • Influenza A virus NEP (NS2 protein) downregulates RNA synthesis of model template RNAs. (
  • A new method for reconstituting influenza polymerase and RNA in vitro: a study of the promoter elements for cRNA and vRNA synthesis in vitro and viral rescue in vivo. (
  • A TK-virus requires TTP for DNA synthesis from the nucleotide pool present in dividing cells. (
  • Viral replication is blocked at a late stage of virion assembly, so, importantly, viral and recombinant protein synthesis is unimpaired. (
  • For a more precise investigation of how H5 contributes to DNA synthesis, we placed the ts57 H5 allele in an otherwise wild-type viral background and also performed small interfering RNA-mediated depletion of H5. (
  • By generating an H5-expressing cell line, we were able to isolate a deletion virus that lacks the H5 gene and show definitively that genome synthesis does not occur in the absence of H5. (
  • Implicit in this discussion was the choice of a broad definition of DNA replication, one which centers on DNA synthesis but also encompasses regulation of the topology of genomic DNA and its assembly into a nucleoprotein complex. (
  • Accordingly, viral protein synthesis was significantly reduced by PI3K inhibition. (
  • Viral protein synthesis was also enhanced in cells overexpressing the constitutively active Akt1. (
  • Amino acids play an important role in virus-related infections as they are needed for protein synthesis and they also regulate many metabolic pathways, including gene expression. (
  • Arginine is not involved in the early steps of virus replication at the level of viral DNA synthesis. (
  • It is necessary before the synthesis of virus DNA and the second requirement is associated with the formation of mature virions. (
  • In the absence of arginine, viral DNA synthesis continues undisturbed, whereas the formation of virions is inhibited. (
  • I5 synthesis was dependent on viral DNA replication and occurred exclusively at late times, consistent with a consensus late promoter motif adjacent to the start of the open reading frame. (
  • Biochemical and confocal microscopic studies indicated that A43 is expressed at late times following viral DNA synthesis and is a type-1 membrane protein with two N-linked oligosaccharide chains. (
  • Vaccinia virus displayed increased cytotoxicity in some hypoxic cancer cells even though viral protein synthesis and transgene expression were not affected. (
  • The viral replication, protein synthesis and assembly require a considerable amount of energy, provided by large clusters of mitochondria at the periphery of viroplasms. (
  • Vaccinia virus is member of Orthopoxvirus family. (
  • The high-resolution structure that has been obtained of components of the vaccinia virus DNA replication machinery will facilitate the development of drugs and help to understand orthopoxvirus drug resistance. (
  • Modified vaccinia virus Ankara (MVA) is an attenuated vaccinia strain with large deletions of the parental genome that render it non-replicative in mammalian cells. (
  • Constructed in the Modified Vaccinia Ankara (MVA) vector, GEO-LM01 expresses the glycoprotein precursor (GPC) and zinc-binding matrix protein (Z) from the prototype Josiah strain lineage IV. (
  • Our laboratory has explored the application of tumor-selective replicating vaccinia virus (WR strain) for cancer therapy ( 4 , 9 ). (
  • The Copenhagen strain of vaccinia virus only has a truncated version of this protein. (
  • RT "Nucleotide sequence of 42 kbp of vaccinia virus strain WR from near RT the right inverted terminal repeat. (
  • MVA is a highly attenuated strain of vaccinia virus that is unable to replicate efficiently in human cell lines and most mammalian cells. (
  • The attenuated vaccinia Tian Tan strain Guang 9 (VG9), with active yeast CD expression and thymidine kinase (TK) deficiency, was successfully constructed. (
  • This strain does not carry mouse mammary tumor virus (MMTV). (
  • Interaction between immune checkpoint inhibitors and oncolytic virotherapy was found to be complex, with correct selection of viral strain, antibody, and timing of the combination being critical for synergistic effects. (
  • Two major DNA variants present in serially propagated stocks of the WR strain of vaccinia virus," J. of Virology 37:1000-1010 (1981). (
  • Modified vaccinia virus Ankara (MVA) is an attenuated vaccinia virus that was developed through serial passaging in chicken embryonic fibroblasts. (
  • MVA-HPV is a modified vaccinia virus Ankara vector (MVA). (
  • These data support a role for cathelicidins in the inhibition of orthopox virus (vaccinia) replication both in vitro and in vivo. (
  • Taken together, our results demonstrate that APOBEC3D/F and APOBEC3G fundamentally work as restriction factors against HIV-1 in vivo, but at the same time, that APOBEC3D and APOBEC3F are capable of promoting viral diversification and evolution in vivo. (
  • This study aims to determine the in vivo biodistribution, and imaging and timing characteristics of a vaccinia virus, GLV-1h153, encoding the human sodium iodide symporter (hNIS. (
  • In vivo, biodistribution profiles revealed persistence of virus in tumors 5 weeks postinjection at 10\(^9\) plaque-forming unit (PFU)/gm tissue, with the virus mainly cleared from all other major organs. (
  • A single immunization elicited potent humoral, T-helper, and cytotoxic T-cell immune responses in mice despite the absence of any detectable virus replication in vivo. (
  • Then, in vitro and in vivo antitumor efficacy of vaccinia VG9-CD plus 5-FC administration was evaluated in colorectal cancer cells. (
  • What we hope to achieve ultimately is to identify NLRX1 small compound inhibitors, which may help to remove HIV-1 virus in vivo ," Guo told SpectroscopyNOW. (
  • We demonstrated that ex vivo CD8+ T cell viral inhibitory activity measured in HIV-positive patients is correlated with viral load set-point and is predictive of the rate of HIV disease progression. (
  • Conclusions: This is the first study to demonstrate that TNBCs are killed by a novel vaccinia virus both in vitro and in vivo. (
  • Boyle DB, Coupar BE, Gibbs AJ, Seigman LJ, Both GW (1987) Fowlpox virus thymidine kinase: nucleotide sequence and relationships to other thymidine kinases. (
  • Idoxuridine, a pyrimidine nucleoside structurally related to thymidine, inhibits viral replication by substituting itself for thymidine in viral DNA. (
  • Thymidine kinase (TK) in vaccinia virus, is an enzyme needed for nucleic acid metabolism. (
  • Mapping of the vaccinia virus thymidine kinase gene by marker rescue and by cell-free translation of selected mRNA" Proc. (
  • Biopsy samples analyzed by PCR identified the presence of the JX-594-specific hGM-CSF transgene and the disrupted viral thymidine kinase gene. (
  • The virus cannot infect noncancerous cells, Kirn explained, because researchers deleted its thymidine kinase gene, which it needs to replicate in the body. (
  • 1. An infectious bovine rhinotracheitis virus which fails to produce any functional thymidine kinase as a result of an insertion in the thymidine kinase gene. (
  • 4) selecting or screening, in tk - IBRV host cells, for tk - IBRV from the virus produced in step (3) so as to produce an infectious bovine rhinotracheitis virus mutant which fails to produce any functional thymidine kinase as a result of an insertion in the IBRV tk gene. (
  • 5) propagating the resulting infectious bovine rhinotracheitis virus mutant of step (4) at a non-permissive temperature for a temperature-sensitive virus so as to select for and produce a temperature-resistant infectious bovine rhinotracheitis virus mutant which fails to produce any functional thymidine kinase as a result of an insertion in the IBRV tk gene. (
  • This is the first report showing that a single dose of a replication-deficient MVA vector can confer full protection against a lethal challenge with ML29 virus. (
  • Zika virus (ZIKV) is one of the recently emerging vector-borne viruses in humans and is responsible for severe congenital abnormalities such as microcephaly in the Western Hemisphere. (
  • Replication-deficient recombinant MVA has been seen as an exceptionally safe viral vector. (
  • Transgene's programs utilize viral vector technology with the goal of indirectly or directly killing infected or cancerous cells. (
  • The open reading frame was cloned into a pET11c expression vector and the partially purified recombinant protein was shown to have specificity for single-stranded DNA as well as stimulate vaccinia RR activity. (
  • A method of inducing expression of immune active cytokines in tumors in situ is provided wherein a vaccinia virus vector capable of inducing expression of a selected cytokine is generated and injected into a tumor so that cells of the tumor express the selected cytokine. (
  • Bovine papilloma virus deoxyribonucleic acid: a novel eukaryotic cloning vector. (
  • 5. The transgenic avian of claim 4 , wherein the vector is selected from the group consisting of a plasmid, a viral vector, and an artificial chromosome. (
  • Combining knowledge of immunological responses to viruses and viral evasion of the immune system has led to the creation of several viral vector models targeted to overcome the normal immune response. (
  • 2008). Through the analysis of current research in viral vector mediated gene therapy, it is possible to evaluate the practical and theoretical application of gene therapy through a viral vector as a treatment option for genetic diseases. (
  • At the time of peak viral replication, virus titers in the spleens of pVAX/LAMP/234 immunized mice was a 130-fold lower than that of pVAX (vector control) immunized mice. (
  • In the case of the Cauliflower mosaic virus (CaMV), viroplasms improve the virus transmission by the aphid vector. (
  • Vaccinia virus encodes two more serpin - SPI-1 and SPI-3. (
  • RT "Vaccinia virus encodes a polypeptide with DNA ligase activity. (
  • Deletion of a 9,000 base-pair segment of the vaccinia virus genome that encodes nonessential polypeptides," J. of Virology 40:387-395 (1981). (
  • The vaccinia virus I5L open reading frame encodes a 79-amino-acid protein, with two predicted transmembrane domains, conserved among all sequenced members of the chordopoxvirus subfamily. (
  • The vaccinia virus A43R open reading frame encodes a 168-amino acid protein with a predicted N-terminal signal sequence and a C-terminal transmembrane domain. (
  • When administered to animals, vSP retains full ability to replicate in tumor tissues, whereas replication in normal tissues is greatly diminished. (
  • Virus-associated toxicity is a concern and various modifications have been explored in an effort to improve both tumor specificity and safety profiles ( 1 ). (
  • In tumor models in mice, the TK/VGF double-deletion mutant displayed higher tumor-targeting capacity and potent tumoricidal activity with reduced viral pathogenicity ( 10 ). (
  • These results tell us that in order for viral-based therapy to work, it has to engage the host immune system through induction of innate immunity and activation of tumor antigen-presenting dendritic cells," she added. (
  • Pexa-Vec (JX-594) is an oncolytic immunotherapeutic based on an oncolytic vaccinia virus armed with a GM-CSF gene that promotes an anti-tumor immune response. (
  • Viral cytotoxicity and tumor regression of treated PANC-1tumor xenografts in nude mice was also determined. (
  • Vaccinia viruses have emerged as attractive therapeutic candidates for cancer treatment due to their inherent ability of tumor tropism and oncolytic property. (
  • Vaccinia virus armed with the prodrug-activator CD gene would result in augmented antitumor effects that combined the effect of vaccinia virus and 5-FU together, and particularly limited the anticancer drug to tumor regions. (
  • In colorectal tumor models, mice treated with vaccinia VG9-TK − showed better tumor remission ability and prolonged survival. (
  • Furthermore, oncolytic viruses prevent tumor recurrence via the induction of long-term immunological memory [ 13 ]. (
  • Deletion of the TK gene inhibits viral replication in normal non-dividing cells, however, tumor cells have an increased pool of functional nucleotides allowing vaccinia virus replication in the absence of viral TK [ 19 ]. (
  • CD-armed vaccinia virus, in conjunction with subsequent 5-FC, provides direct killing of tumor cells by local production of 5-FU. (
  • Despite the lack of exogenous mouse mammary tumor virus (MMTV), virgin and breeding females may still develop some mammary tumors later in life. (
  • This high incidence resulted from exogenous mouse mammary tumor virus (MMTV) transmitted through the mother's milk. (
  • A period of oncolytic viral replication and directed targeting of the immune response against the tumor were required for the most beneficial effects, with CD8 + and NK, but not CD4 + cells mediating the effects. (
  • Pexa-Vec (JX594/TG6006 - pexastimogene devacirepvec) is an oncolytic immunotherapy product based on an oncolytic vaccinia virus armed with a GM-CSF gene that promotes an anti-tumor immune response. (
  • Lysis of vaccinia virus-infected tumor cells results as a consequence of viral replication combined with tumor specific immunity that is enhanced by JX594-derived granulocyte macrophage-colony stimulating factor (GM-CSF). (
  • The application of oncolytic viruses is a potential strategy for controlling advanced-stage cancer because intratumoral (i.t.) injection of an oncolytic virus, such as vaccinia virus, results in tumor cell lysis and subsequent release of tumor antigens into the microenvironment. (
  • In the current study, we hypothesize that in tumor-bearing mice primed with DNA encoding an immunogenic foreign antigen, ovalbumin (OVA) followed by a boost with i.t. administration of vaccinia virus encoding the same foreign antigen, OVA, can generate enhanced antitumor effects through the combination of viral oncolysis and tumor-specific immunity. (
  • We observed that tumor-bearing mice primed with OVA DNA and boosted with vaccinia encoding OVA (Vac-OVA) generated significant therapeutic antitumor effects as well as induced significant levels of OVA-specific CD8 + T cells in two different tumor models. (
  • Our study aims to investigate an innovative strategy to enhance therapeutic antitumor effects through viral oncolysis and tumor-specific immunity. (
  • Furthermore, oncolytic vaccinia virus has been shown to preferentially infect tumor cells over surrounding normal tissues in several cancer models ( 6 - 8 ). (
  • recently showed that vaccinia virus administered to mice i.p. can preferentially infect ovarian tumor cells but not normal tissue and generates significant antitumor responses based on a noninvasive luminescence imaging system, which facilitates monitoring of cancer cell proliferation and growth ( 9 ). (
  • Thus, vaccinia represents a promising agent for viral-mediated tumor oncolysis as well as immunomodulatory gene delivery to advanced cancer cells. (
  • Intratumoral (i.t.) injection of vaccinia also represents a potentially promising approach to generate tumor-specific immunity. (
  • Vaccinia may directly cause tumor cell lysis, which can lead to the release of tumor antigens into the microenvironment. (
  • Some oncolytic viruses are better adapted than others to the hypoxic tumor environment. (
  • However, vesicular stomatitis virus and reovirus, but not encephalomyocarditis virus, are sensitive to elevated levels of hypoxia-inducible factor-1α in renal cancer cells with the loss of von Hippel-Lindau tumor suppressor protein, because elevated hypoxia-inducible factor activity confers dramatically enhanced resistance to cytotoxicity mediated by vesicular stomatitis virus or reovirus. (
  • It is envisioned that further improved oncolytic viruses will be highly effective against hypoxic tumor, especially when combined with other therapeutic regimens such as immunotherapy, radiation therapy, and/or chemotherapy. (
  • The three-way interaction between oncolytic viruses, the tumor microenvironment, and the immune system is critical to the outcome of antitumor therapy. (
  • In this review we discuss the ability of oncolytic viruses to alter the immunogenic milieu of the tumor microenvironment, and the role of innate and adaptive immunity in both restricting and augmenting therapy. (
  • This immune-mediated therapy is induced, they would argue, by viral triggering of potent antitumoral immune effectors that destroy both infected (the minority) as well as uninfected (the majority) tumor cells. (
  • These studies will show whether the responses that control increased viral replication can be selectively inhibited, while the responses that lead to immune-mediated tumor cell killing can be selectively augmented. (
  • Oncolytic viruses are self-replicating, theoretically tumor selective, and possess an ability to directly lyse cancer cells. (
  • On the basis of the concept that tumor-selective replication will amplify viral load enhancing antitumor efficacy, while sparing normal tissues, oncolytic viruses represent a very attractive novel approach to cancer therapy. (
  • Is the Subject Area "Viral gene expression" applicable to this article? (
  • Outcomes included quantification of viral PFU, vaccinia viral gene expression by quantitative real-time RT-PCR, and changes in virion structure by transmission electron microscopy. (
  • Replication generates progeny genomes and initiates the transition to late gene expression. (
  • Overall, our data show that both PI3K and Akt1 play a role in viral gene expression, leading to an increase in virus replication. (
  • Animal viruses are providing scientists with relatively simple models to study the molecular biology of genome replication and gene expression. (
  • Whereas viruses use, in general, pathways of macromolecular biosynthesis common to the host cell, they have a cunning ability to adopt unusual mechanisms of gene expression and gene replication, provided these special pathways offer an advantage in competition for cellular resources. (
  • Any study of viral gene expression and replication is likely to lead also to new insights in cellular metabolism. (
  • Structural and functional characterization of an influenza virus RNA polymerase-genomic RNA complex. (
  • Influenza virus naked RNA can be expressed upon transfection into cells co-expressing the three subunits of the polymerase and the nucleoprotein from simian virus 40 recombinant viruses. (
  • The crystal structure of the DNA polymerase of the prototype vaccinia virus is reported here. (
  • The crystal structure determination of vaccinia virus polymerase was challenging due to the radiation sensitivity of the long needle-like DNA polymerase crystals obtained from low amounts of protein produced in insect cells. (
  • Overall structure of vaccinia virus DNA polymerase showing the canonical domains of family B polymerases. (
  • Left panel) Model of the vaccinia virus DNA polymerase in elongation mode with bound template strand (blue), the newly synthesised strand (cyan) and the incoming nucleotide in space-filling representation (magenta). (
  • The domain movements in the model, compared to the crystallised DNA-free form, were confirmed using SAXS (right panel, calculated curve from the DNA-free model in blue, from the DNA-bound model in red, experimental points from the vaccinia virus polymerase/DNA complex in black). (
  • Here we show that H5 localizes to replication factories, as visualized by immunofluorescence and immunoelectron microscopy, and can be retrieved upon purification of the viral polymerase holoenzyme complex. (
  • Berns KI, Silverman C, Weissbach A (1969) Separation of a new deoxyribonucleic acid polymerase from vaccinia-infected HeLa cells. (
  • Binns MM, Stenzler L, Tomley FM, Campbell J, Boursnell MEG (1987) Identification by a random sequencing strategy of the fowlpoxvirus DNA polymerase gene, its nucleotide sequence and comparison with other viral DNA polymerases. (
  • Challberg MD, Englund PT (1979a) Purification and properties of the deoxyribonucleic acid polymerase induced by vaccinia virus. (
  • Challberg MD, Englund PT (1979b) The effect of template secondary structure on vaccinia DNA polymerase. (
  • Citarella RV, Muller R, Schlabach A, Weissbach A (1972) Studies on vaccinia virus-directed deoxyribonucleic acid polymerase. (
  • A complete cDNA clone of the genome (15,246 nucleotides) of the paramyxovirus SV5 was constructed from cDNAs such that an anti-genome RNA could be transcribed by T7 RNA polymerase and the correct 3' end generated by cleavage using hepatitis delta virus ribozyme. (
  • The gene encoding bacteriophage T7 RNA polymerase (T7gene1) was placed under the control of regulatory elements from the Escherichia coli lac operon to construct an inducible vaccinia virus expression system consisting entirely of prokaryotic transcriptional machinery. (
  • Wrapping the viroplasm with a membrane, concentrates the viral components required for the genome replication and the morphogenesis of new virus particles, so it increases the efficiency of the processes. (
  • pDCs are potent type I interferon (IFN) producing cells that sense viral infections via TLR7, TLR8, and TLR9, and their adaptor MyD88 [15] . (
  • Viral infections occur after entrance of virions into host cells by a variety of mechanisms, including endocytosis of nonenveloped viruses and fusion with the cell membrane by enveloped viruses ( 1 ). (
  • Zika virus was initially isolated from Uganda in 1947 and viral infections only occurred sporadically in Africa and Asia until 2007. (
  • Together, our findings identify an unprecedented paracrine and/or systemic function of placental trophoblasts that uses exosome-mediated transfer of a unique set of placental-specific effector miRNAs to directly communicate with placental or maternal target cells and regulate their immunity to viral infections. (
  • Arginine is an essential requirement for the replication of viruses and progression of viral infections. (
  • In recent years, the number and severity of DENV human infections have increased due to the expanded geographic range of the virus. (
  • Animal-borne orthopoxviruses, like monkeypox, vaccinia and the closely related cowpox virus, are all capable of causing zoonotic infections in humans, representing a potential threat to human health. (
  • It may be speculated that these differences at the cellular level contribute to the individual characteristics of cowpox, monkeypox and vaccinia virus infections in certain host species. (
  • most other viruses replicate within the cell nucleus. (
  • To test this, the researchers compared the antitumor efficacy of live oncolytic vaccinia virus (which can replicate) with its heat-inactivated counterpart (which cannot replicate) in mice. (
  • Poxviruses are large, complex, double-stranded DNA viruses that replicate in the cytoplasm of infected cells ( 1 ). (
  • A single virus particle (virion) cannot replicate or express genetic material (DNA, RNA) without a host cell. (
  • When the engineered viruses recognize and infect cancer cells, they replicate and sometimes destroy their hosts. (
  • Orthopoxviruses are large double-stranded DNA viruses that are unique amongst DNA viruses in that they replicate exclusively within the cytoplasm of infected cells. (
  • Viable I5L deletion and frameshift mutants were constructed and found to replicate like wild-type virus in a variety of cell lines, indicating that the protein was dispensable for in vitro cultivation. (
  • Viruses are considered as extremely successful predators as they can replicate and control the host cell synthesizing machinery. (
  • Viroplasms have been reported in many unrelated groups of Eukaryotic viruses that replicate in cytoplasm, however, viroplasms from plant viruses have not been as studied as viroplasms from animal viruses. (
  • Possible bioterrorism with smallpox has led to the resumption of smallpox (vaccinia virus) immunization. (
  • It was shown that immunization with vaccinia virus with deleted SPI-2 and 1 and coexpressing IFNγ leads to strong attenuation but without decreasing host immune response. (
  • All studies on animal viruses potentially lead to the development of tools for their control, be it through prevention by immunization or treatment with antiviral drugs. (
  • Delivery of this epitope to BALB/c mice by vaccinia virus resulted in protective immunity but only partial protection was reported following immunization with a pp89 expression plasmid alone. (
  • Taken together, these results demonstrated that immunization with pVAX/LAMP/234 chimeras significantly reduce viral titers in target organs. (
  • Structure and assembly of intracellular mature vaccinia virus: thin-section analyses. (
  • Structure and assembly of intracellular mature vaccinia virus: isolated-particle analysis. (
  • Dahl R, Kates JR (1970) Intracellular structures containing vaccinia DNA: isolation and characterization. (
  • Viruses can exist in two forms: extra cellular virion particles and intracellular genomes. (
  • The model describes the interaction of uninfected target cells, infected cells, free viruses and humoral immune response, incorporating two virus transmission modes and intracellular delay. (
  • For example, the vaccinia B1 kinase plays a vital role in inactivating the cellular antiviral factor BAF, and is suggested to orchestrate other pathways. (
  • In this study, we evaluated ATA as a potential antiviral drug against ZIKV replication. (
  • Not only do we realize viruses have many immune-evasion strategies to escape NK cell responses, but that stimulation of NK cell subsets during an antiviral response occurs through receptors seemingly geared directly at viral products and that NK cells can provide a memory response to viral pathogens. (
  • conclude that the effective control of vaccinia virus may hinge on an antimicrobial peptide called cathelicidin LL-37, which has been shown to have direct antiviral properties in vitro. (
  • Even though there is no particular treatment or therapy for HIV, very effective treatment called antiviral therapy, combination therapy, or HAART (highly active antiretroviral therapy) can retain the virus under control and permit someone with HIV to have an active, health life. (
  • The genome of Rabies virus, Borna disease virus and Ebola virus code for the P phosphoprotein and VP35 that can block the antiviral response induced by IFN [ 8 , 9 , 10 ]. (
  • It is possible that the IFN-γ expressed by rVACVs induces both an antiviral state and increased immunological clearance, thus resulting in decreased levels of antigen expression due to reduced viral replication and spread. (
  • Entry of the two infectious forms of vaccinia virus at the plasma membane is signaling-dependent for the IMV but not the EEV. (
  • The dormant nature of these viruses may be explained by the availability of arginine during various stages of the infectious process. (
  • Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892. (
  • Detecting nucleic acids such as DNA is an important part of recognizing pathogens and infectious agents, particularly viruses, and activating the innate immune system. (
  • 2. The infectious bovine rhinotracheitis virus as claimed in claim 1, wherein said insertion is about 8 to 5000 bp in size. (
  • 3. The infectious bovine rhinotracheitis virus as claimed in claim 1, wherein said insertion is a foreign gene which is inserted in a manner such that it is not expressed by said virus. (
  • 4. The infectious bovine rhinotracheitis virus as claimed in claim 1, wherein said virus is also temperature-resistant. (
  • 5. The infectious bovine rhinotracheitis virus as claimed in claim 1, wherein said virus has the identifying characteristics of IBRV(βGalINV) (ATCC No. VR 2160). (
  • 10. The infectious bovine rhinotracheitis virus as claimed in claim 7, wherein the infectious DNA of step (3) is derived from a temperature-resistant infectious bovine rhinotracheitis virus such that the resulting mutant of step (4) is also temperature-resistant. (
  • 0.001), and alteration of vaccinia virion structure. (
  • Through the use of transient expression assays and directed genetics, the vaccinia virus (VV) I7L gene product has been implicated as the major maturational proteinase required for viral core protein cleavage to occur during virion assembly. (
  • Membrane fusion utilizes a membrane envelope surrounding the virus to fuse with the membrane of the host, allowing the entire virion entry into the host cell. (
  • Poxviruses employ sophisticated signaling pathways that thwart cellular defense mechanisms and simultaneously ensure viral factors are modulated properly. (
  • B1 is highly conserved among poxviruses and exhibits a remarkable degree of similarity to VRKs, a family of cellular kinases, suggesting that the viral enzyme has evolved to mimic VRK activity. (
  • Then using this virus, we tested the hypothesis that cellular VRKs can complement B1 function, and discovered a VRK2 role in facilitating DNA replication in the absence of B1. (
  • Vaccinia-virus-induced cellular contractility facilitates the subcellular localization of the viral replication sites. (
  • Vaccinia virus-induced microtubule-dependent cellular rearrangements. (
  • The study of vaccinia virus thus provides important information that will help us to understand the nature of more pathogenic members of the family, such as the agents of smallpox, monkeypox, and molluscum contagiosum ( 10 ), as well as insights into many areas of molecular and cellular biology and immunology. (
  • Comparative examination of viral and host protein homologs reveals novel mechanisms governing downstream signaling effectors of both cellular and vi- ral origin. (
  • The vaccinia virus B1 protein kinase is involved in promoting multiple facets of the virus life cycle and is a homolog of three conserved cellular enzymes called vaccinia virus-related kinases (VRKs). (
  • RT "Vaccinia virus DNA ligase recruits cellular topoisomerase II to sites RT of viral replication and assembly. (
  • cGAMP (c[G(2′,5′)pA(3′,5′)p])] produced by a cellular nucleotidyltransferase referred to as cGAS (cyclic GMP-AMP synthase, Mab-21 domain-containing protein or C6orf150) following its association with nucleic acid species such as viral DNA ( 10 ). (
  • My research with vaccinia virus has led to the discovery that during replication of the viral DNA, vaccinia must evade a cellular protein called BAF, which would otherwise bind to the viral DNA and inhibit its replication. (
  • They found that the recombinant virus containing the introduced K1L gene prevented degradation of the cellular inhibitor of NF-kB, therefore inhibiting NF-kB s ability to ignite immune responses. (
  • By replacing pieces of a viral genome with a known genetic sequence, harnessing the viral lifecycle allows the capability to carry the new viral sequence across the cell membrane and bring the modified genome in contact with a defective cellular genome. (
  • Following cellular attachment, it is necessary for the genome of the virus to be moved inside the cell. (
  • There are certain cellular components which are manipulated by viruses to evade the innate immune response. (
  • Specifically promotes translation of a subset of viral and cellular mRNAs carrying a 5'proximal stem-loop structure in their 5'UTRs and cooperates with the eIF4F complex. (
  • The recruitment of cellular membranes and cytoskeleton to generate virus replication sites can also benefit viruses in other ways. (
  • Aggregated structures may protect viral functional complexes from the cellular degradation systems. (
  • A single intramuscular dose of GEO-LM01 protected 100% of CBA/J mice challenged with a lethal dose of ML29, a Mopeia/Lassa reassortant virus, delivered directly into the brain. (
  • CRAMP knockout mice and control animals were inoculated by skin pricks with 2 × 10 5 PFU of vaccinia and examined daily for pox development. (
  • In a model of viral pathogenesis, mice treated with vSP survived substantially longer when compared with mice treated with the wild-type virus. (
  • We recently determined that TLR3 regulates a detrimental innate immune response that enhances replication, morbidity, and mortality in mice in response to vaccinia virus, a model pathogen for studies of poxviruses. (
  • Challenge of primary bone marrow macrophages isolated from TLR4 mutant and control mice suggested that TLR4 recognizes a viral ligand rather than an endogenous ligand. (
  • Moreover, single genome sequencing analyses of viral RNA in plasma of infected mice reveal that 4A HIV-1 is specifically and significantly diversified. (
  • Furthermore, a mutated virus that is capable of using both CCR5 and CXCR4 as entry coreceptor is specifically detected in 4A HIV-1-infected mice. (
  • These rVACVs replicated to high titers in tissue culture, yet were avirulent in both immunocompromised and immunocompetent mice with no detectable viral replication in these animals. (
  • Mice lacking a homolog of LL-37 also showed poor control of vaccinia replication. (
  • Although the A43 mutant produced significantly smaller lesions in the skin of mice than the control, the amounts of virus recovered from the lesions were similar. (
  • However, TRIF−/− mice differed from TLR3−/− animals in that replication of Vac-GFL was greater in mice lacking TRIF, as quantified by region of interest analysis of head, chest, and abdomen sites on bioluminescence images. (
  • These data indicate that a different and/or additional host molecule(s) controls responses to vaccinia in TRIF−/− mice relative to those mediated solely by TLR3. (
  • Effects of post-challenge administration of ST-246 on dissemination of IHD-J-Luc vaccinia virus in normal and in immune deficient mice reconstituted with T cells. (
  • Areas Under the flux Curve (AUC) were calculated for individual mice to assess viral loads. (
  • Two to five days treatment of normal BALB/c mice with ST-246 at 100 mg/kg starting 24 hr post challenge conferred 100% protection and reduced viral loads in 4 organs compared with control mice. (
  • Mice also survived after 5-day treatment with 30 mg/kg of ST-246, yet viral loads and poxes were higher in these mice compared with 100 mg/kg group. (
  • Two of the most promising novel therapeutic platforms for the treatment of cancer are blockade of immune checkpoints and oncolytic viral therapies. (
  • The study shows that priming with DNA encoding foreign antigen followed by intratumoral injection of vaccinia encoding the same foreign antigen leads to significant therapeutic antitumor effects through the combination of viral oncolysis as well as antigen-specific T cell-mediated killing. (
  • Objective: This study aimed to investigate the therapeutic impact of a new oncolytic vaccinia virus in a triple-negative breast cancer (TNBC) murine model and its potential for treating distant metastatic disease. (
  • DOI PubMed Moller-Larsen A, Haahr S. Humoral and cell-mediated immune responses in humans before and after revaccination with vaccinia virus. (
  • If we can find out how the virus evades immune responses and learn more about the signals the virus sees as necessary for replicating within the host cell, then we can figure out how to inhibit them and halt the viral replication," she said. (
  • These include postvaccinial central nervous system disease, progressive vaccinia, eczema vaccinatum, accidental implantations, "generalized vaccinia," and the common erythematous and/or urticarial rashes. (
  • Progressive vaccinia in a patient with acute myeloid leukemia. (
  • Detection of nucleic acids is crucial in triggering the innate immune to pathogens, particularly in response to viruses ( Pichlmair and Reis e Sousa, 2007 ). (
  • The virus particles appear brick-shaped & are made of a complex structure of membranes surrounding the genetic core of DNA - the nucleoid. (
  • Genetic Confirmation that the H5 Protein Is Required for Vaccinia Virus DNA Replication. (
  • Researchers have categorized the HIV-1 virus into groups, subtypes and sub-subtypes that classification is based on the genetic variation and phylogenetic analysis . (
  • One current gene therapy treatment possibility is utilizing viruses to alter the incorrect genetic sequence in diseased individuals. (
  • Researchers have been able to isolate viruses, remove pathogenic genetic sequences, insert a useful treatment sequence and achieve positive results in animal models. (
  • It is a member of the nucleoside antimetabolite drugs that interfere with duplication of viral genetic material. (
  • Advances in virus manufacture, genetic engineering, and cell biology have led to a surge of interest in the use of viruses for cancer therapy. (
  • When expressed together, GP and Z form Virus-Like Particles (VLPs) in cell culture. (
  • The absence of essential amino acids may result in empty virus particles that are free of viral nucleic acids (DNA or RNA). (
  • this was explained by their weak micromolar affinity for virus particles. (
  • In animal cells, virus particles are gathered by the microtubule-dependent aggregation of toxic or misfolded protein near the microtubule organizing center (MTOC), so the viroplasms of animal viruses are generally localized near the MTOC. (
  • MVA is an attenuated form of vaccinia virus that has undergone 570 passages in primary chicken embryo fibroblasts and has genomic deletions that reduce its pathogenicity ( 23 ). (
  • Screening a lambda phale expression library of vaccinia with the anti-idiotypic antibody localized the binding site to the carboxy terminal 81 amino acids in open reading frame 1-3 of the vaccinia genome. (
  • Later this year, the company plans to launch a phase III clinical trial in advanced liver cancer patients, in which the virus will be added to standard antibody treatment. (
  • Targeting the conserved stalk region of the influenza virus hemagglutinin (HA), the major glycoprotein on the surface of the virus, results in the production of broadly protective antibody responses. (
  • Viruses have evolved several methods to avoid immune system recognition, including breaking down major histocompatibility (MHC) molecules, interrupting cytokine signaling and avoiding antibody binding. (
  • This study aimed to determine if insertion of the human sodium iodide symporter (hNIS) cDNA as a marker for non-invasive imaging of virotherapy alters the replication and oncolytic capability of a novel vaccinia virus, GLV-1h153. (
  • Conclusion: Insertion of the hNIS gene does not hinder replication or oncolytic capability of GLV-1h153, rendering this novel virus a promising new candidate for the noninvasive imaging and tracking of oncolytic viral therapy. (
  • Moreover, vaccinia VG9-CD in combination with gavage administration of 5-FC displayed the best antitumor efficacy, especially for the prolongation of survival. (
  • Little information is available regarding whether an oncolytic therapy, such as based on HSV1, will exert efficacy in a patient, as the molecular mechanisms explaining viral oncolysis remain to be clarified. (
  • By analyzing features of epitope-specific CD8 T cell responses escaped to differing extents/with differing kinetics, we were able to gain insight into the interacting factors that determine CTL escape, providing evidence that escape is restricted by viral fitness constraints and is promoted when a response makes a particularly dominant contribution to control of viral replication (due to its magnitude and/or efficacy). (
  • Classically, the immune system is thought to limit the efficacy of therapy, leading to viral clearance. (
  • Xie, Zhixun 2014-08-01 00:00:00 We have previously reported that inhibition of phosphatidylinositol 3-kinase (PI3K) reduces porcine reproductive and respiratory syndrome (PRRSV) replication. (
  • Here, we further investigate the mechanism by which PI3K inhibition affects virus replication and the role of Akt1 kinase in virus replication. (
  • We found that PI3K inhibition reduced viral gene transcription by approximately 1.5-fold. (
  • The realization that inhibition of immune checkpoints is a critical need for successful immunotherapy and that the immune response activated by oncolytic viral therapies provide their most potent antitumor effects, means that the combination of these approaches is likely to result in significant clinical benefit. (
  • Antitumor effects attributable to virus-mediated cell death are observed ( 1 , 6 - 8 ). (
  • It is not known whether viral replication is necessary for the antitumor effects of the DNA virus when delivered intratumorally. (
  • Arming vaccinia virus with a prodrug-activator gene might result in augmented antitumor effects that combined the effect of vaccinia virus and chemotherapy together, but with less systemic toxicity [ 25 ]. (
  • More recently, immuno-oncologists have suggested that the very same "baby" may be central to the ability of the virus to generate antitumor therapy. (
  • Although the exact origins of vaccinia virus are uncertain, vaccinia may represent a hybrid of the variola and cowpox viruses. (
  • The vaccinia virus causes cowpox, a disease of cattle & humans that causes skin lesions resembling those of smallpox, but without the associated systemic disturbances. (
  • SPI-2 shares 92% of its amino acid sequence with the cowpox virus modifier of the cytokine response - known as crmA. (
  • The vaccinia virus has been developed by the biotechnology company Jennerex-named after Edward Jenner, who in the 18th century discovered that a cowpox virus could inoculate against smallpox. (
  • These large DNA viruses encode for many of their own enzymes of DNA metabolism, including a small type IB topoisomerase (vTopo) that is closely related to the human type I topoisomerase (hTopo) ( Shuman, 1998 ). (
  • Variola virus (the causative agent of smallpox) and monkeypox virus are important human pathogens [1] - [3] . (
  • The variola virus causes smallpox and may have begun infecting humans approximately 10,000 years ago. (
  • This effort was successful for several reasons, including the lack of any natural reservoir for variola virus and the ease of identifying infected individuals. (
  • The threat of a bioterrorist attack using Variola major , the smallpox virus, or zoonotic transmission of other poxviruses has renewed interest in understanding interactions between these viruses and their hosts. (
  • For example, while variola virus caused only a mild and localized disease in some individuals, many succumbed to severe disease with very high mortality rates especially for some strains of the virus (reviewed in Bray and Buller, 2004 ). (
  • IMPORTANCE: Variola virus, the causative agent of smallpox, is the most notorious member of the Poxviridae family. (
  • Viruses in this family are the cause of numerous diseases including smallpox (variola), and recent human outbreaks of monkeypox. (
  • FUNCTION: DNA ligase that seals nicks in double-stranded DNA CC during DNA replication, DNA recombination and DNA repair. (
  • Replication of double stranded viral DNA occurs in very discrete loci in infected cells and these DNA factories can be isolated from gently lysed cell in sucrose gradients. (
  • Poxviruses are double-stranded DNA viruses capable of causing disfiguring and deadly disease in a wide range of hosts , from insects to mammals. (
  • Viruses of the family Poxviridae are characterized by their large and complex virions, a double-stranded DNA genome of 130-375 kbp and the cytosol as the place of replication [ 1 ]. (
  • The temperature-sensitive (ts) mutant Dts57, which was generated by chemical mutagenesis and has a lesion in H5, exhibits defects in DNA replication and morphogenesis under nonpermissive conditions, depending upon the experimental protocol. (
  • I7L is an essential late gene, as shown through temperature sensitive mutant viruses [ 7 , 8 ] and conditional lethal mutant viruses [ 9 , 10 ] where under non-permissive conditions, viral morphogenesis is blocked prior to the formation of IMV. (
  • Poxviruses are large cytoplasmic DNA viruses that cause human and veterinary diseases. (
  • Orthopox viruses cause a wide range of diseases and even a single type of virus will have a range of clinical course in different individuals. (
  • In order to utilize the viral replication cycle to treat diseases, it is necessary to understand the viral replication cycle. (
  • The aerosol form is used to treat respiratory syncytial virus -related diseases in children. (
  • Human animal viruses may cause diseases ranging from the deadly (AIDS) to the benign (common cold). (
  • Our findings provide insight into the basis for susceptibility to viral oncolysis by agents such as HSV1. (
  • The anti-tumour activity of LIVP-GFP is a result of direct oncolysis of tumour cells in case of melanoma B-16 because the virus effectively replicates and destroys these cells, and virus-mediated activation of the host immune system followed by immunologically mediated destruction of of tumour cells in case of lymphosarcoma RLS-40. (
  • Moreover, this therapy may extend beyond what could realistically be expected from simple viral spread/oncolysis in an immune environment bristling with cells and molecules highly evolved to quench viral replication. (
  • Our data indicate that B12 is not a global repressor, but inhibits vaccinia replication in the absence of the B1 kinase. (
  • First, we demonstrate that vaccinia virus uniquely requires VRK2 for viral repli- cation in the absence of B1, unlike other DNA viruses. (
  • Analysis of vDeltaH5 allowed us to demonstrate conclusively that viral DNA replication is abrogated in the absence of H5. (
  • Ibrahim N, Wicklund A, Jamin A, Wiebe MS . Barrier to autointegration factor (BAF) inhibits vaccinia virus intermediate transcription in the absence of the viral B1 kinase. (
  • Despite the eradication of smallpox virus in 1980, orthopoxviruses, which circulate widely in animals, remain dangerous pathogens. (
  • This recognition leads to the expression of cytokines, chemokines and co-stimulatory molecules that eliminate pathogens like viruses for the activation of antigen presenting cells and for the activation of specific adaptive response [ 4 ]. (
  • Apart from the basic interest in their biology, viruses have gained notoriety, of course, because they are pathogens. (
  • Poxviruses are unique among DNA viruses that infect mammalian cells, in that their replication is restricted to the cytoplasm of the cell. (
  • Transgene (Paris:TNG), a biotech company designing and developing virus-based immunotherapies for the treatment of solid tumors, today announces that the independent Data Monitoring Committee ("IDMC") of the PHOCUS study of Pexa-Vec in Liver Cancer has completed a planned interim futility analysis. (
  • Pexa-Vec is designed to selectively target and destroy cancer cells through three different mechanisms of action: selectively destroy cancer cells through the direct lysis (breakdown) of cancer cells through viral replication, reduce the blood supply to tumors through vascular disruption, and stimulate the body's immune response against cancer cells. (
  • Finally, intratumoral injection of GLV-1h153 facilitated imaging of virus replication in tumors via (124)I-PET. (
  • Within 24 hours we see really impressive replication and spread within tumors. (
  • Replication of vaccinia is the first step to killing cancer cells and shrinking tumors with this approach. (
  • Traditionally, viro-oncologists have perceived the immune system as nothing more than an inhibitor of viral replication through tumors. (
  • RT "Domain structure of vaccinia DNA ligase. (
  • Rescue of SV5 from DNA did not require expression of the viral V protein as a helper plasmid, suggesting that V protein is not essential for initial replication. (
  • In explant studies, patient skin had reduced LL-37 expression and allowed higher levels of viral replication than skin from normal individuals. (
  • otherwise, uncontrolled expression led to interference with endogenous virus replication. (
  • An expression cassette containing a T7 promoter-controlled beta-galactosidase reporter gene was recombined into a different region of the viral genome containing T7gene1. (
  • Addition of increasing amounts of IPTG induced expression of beta-galactosidase to the point of suppression of viral replication. (
  • LIVP-GFP replication, transgene expression and cytopathic effects were analysed in human cervical carcinomas KB-3-1 (MDR−), KB-8-5 (MDR+) and in murine melanoma B-16 (MDR−), murine lymphosarcomas RLS and RLS-40 (MDR+). (
  • Indeed, in three paired normal and transformed cell types, the SPI-1 and SPI-2 gene-deleted virus (vSP) preferentially replicates in transformed cells or p53-null cells when compared with their normal counterparts. (
  • The TK deletion leads to preferential viral replication in dividing cells. (
  • Deletion of this gene causes decreased viral replication in resting cells. (
  • Compared with the wild-type virus, the dual-deletion mutant displayed reduced viral recovery from resting NIH3T3 cells but equivalent viral recovery from dividing NIH3T3 cells in vitro . (
  • They found that the heat-inactivated oncolytic vaccinia virus induced higher numbers of activated CD4+ and CD8+ T cells than the live virus. (
  • In addition, pre-treatment of Vero cells with ATA for up to 72 h also resulted in effective suppression of ZIKV replication with similar IC 50 . (
  • Vaccinia virus infected monkey kidney cells had been previously shown to have an increased ribonucleoside diphosphate reductase (RR) activity. (
  • We show that miRNA members of the chromosome 19 miRNA cluster, which are almost exclusively expressed in the human placenta, are packaged within trophoblast-derived exosomes and attenuate viral replication in recipient cells by the induction of autophagy. (
  • Interestingly, cells overexpressing the dominant negative mutant Akt1 exhibited a significant reduction in viral gene transcription compared to cells overexpressing the constitutively active Akt1. (
  • Vaccinia viruses displayed different oncolytic potency in vitro cells, no relationship with whether they were cancer cells or normal cells. (
  • The result is a 'viral factory' inside cancer cells, Kirn said. (
  • ART stops viral replication but is not able to eliminate cells that harbour dormant (the latent reservoir) HIV. (
  • Scientists at the University of Illinois at Urbana-Champaign studying vaccinia virus, a close relative of smallpox, have determined that a gene necessary for virus replication also has a key role in turning off inflammation, a crucial anti-viral immune response of host cells. (
  • These cells represent an extrahepatic reservoir that can be implicated in virus recurrence and persistence [ 8 , 9 ]. (
  • It was also demonstrated that cells infected during the exponential growth phase gave higher viral yields than those infected during the lag or stationary growth phases and the initial viral MOI did not significantly alter viral yields. (
  • Vesicular stomatitis virus replicated to similar levels in both hypoxic and normoxic conditions, and is effective for killing hypoxic cancer cells. (
  • 1994). They are present not only in all animal and plant cells, as well as microorganisms, but also have been identified in viruses (Ewart et al. (
  • The increase in our understanding of the molecular biology of malignant cells and viruses has now enabled researchers to design viruses that are capable of selectively destroying cancer cells and spare normal surrounding tissue. (
  • The concentration of vaccinia virus is 1.0-5.0 x 10 8 plaque-forming units (PFU)/mL or 2.5-12.5 x 10 5 PFU/dose determined by plaque assay in Vero cells. (
  • Overall, these results demonstrate that ATA has potent inhibitory activity against ZIKV replication and may be considered as a potential anti-ZIKV therapy for future clinical evaluation. (
  • The structure allows an understanding of anti-viral resistance and provides information about the unique mode of processivity factor binding. (
  • Vilona ® ,Virazole ® , also generics from Sandoz, Teva, Warrick) is an anti-viral drug which is active against a number of DNA and RNA viruses . (