Virus Replication: 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.RNA, Viral: Ribonucleic acid that makes up the genetic material of viruses.Viral Proteins: Proteins found in any species of virus.RNA Viruses: Viruses whose genetic material is RNA.Cell Line: Established cell cultures that have the potential to propagate indefinitely.Vaccinia virus: 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.DNA, Viral: Deoxyribonucleic acid that makes up the genetic material of viruses.Molecular Sequence Data: 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.Antiviral Agents: 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.Virus Assembly: The assembly of VIRAL STRUCTURAL PROTEINS and nucleic acid (VIRAL DNA or VIRAL RNA) to form a VIRUS PARTICLE.Sindbis Virus: 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.Virus Cultivation: Process of growing viruses in live animals, plants, or cultured cells.Gene Expression Regulation, Viral: Any of the processes by which cytoplasmic factors influence the differential control of gene action in viruses.Vero Cells: A CELL LINE derived from the kidney of the African green (vervet) monkey, (CERCOPITHECUS AETHIOPS) used primarily in virus replication studies and plaque assays.Receptors, Virus: 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.Defective Viruses: 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.Genes, Viral: The functional hereditary units of VIRUSES.Virus Shedding: 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).HIV-1: The type species of LENTIVIRUS and the etiologic agent of AIDS. It is characterized by its cytopathic effect and affinity for the T4-lymphocyte.Hepatitis B virus: 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.Virus Diseases: A general term for diseases produced by viruses.DNA Viruses: Viruses whose nucleic acid is DNA.Viral Plaque Assay: 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.Base Sequence: The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.Plant Viruses: Viruses parasitic on plants higher than bacteria.Simian immunodeficiency virus: 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.Cytopathogenic Effect, Viral: 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.Measles virus: The type species of MORBILLIVIRUS and the cause of the highly infectious human disease MEASLES, which affects mostly children.Replication Protein A: A single-stranded DNA-binding protein that is found in EUKARYOTIC CELLS. It is required for DNA REPLICATION; DNA REPAIR; and GENETIC RECOMBINATION.Plasmids: 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.Virion: 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.Influenza A Virus, H1N1 Subtype: 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.Influenza A Virus, H5N1 Subtype: 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.Simian virus 40: A species of POLYOMAVIRUS originally isolated from Rhesus monkey kidney tissue. It produces malignancy in human and newborn hamster kidney cell cultures.Amino Acid Sequence: 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.Antigens, Viral: Substances elaborated by viruses that have antigenic activity.Cercopithecus aethiops: 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.Virus Activation: 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.HeLa Cells: 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.Vesicular stomatitis Indiana virus: 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.Virus Latency: 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.Replicon: 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)West Nile virus: 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.Host-Pathogen Interactions: The interactions between a host and a pathogen, usually resulting in disease.Genome, Viral: The complete genetic complement contained in a DNA or RNA molecule in a virus.Mutation: 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.Cells, Cultured: 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.Rabies virus: 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.Viral Nonstructural Proteins: 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.DNA-Binding Proteins: 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.Influenza A Virus, H3N2 Subtype: 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.Recombination, Genetic: 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.Hepacivirus: A genus of FLAVIVIRIDAE causing parenterally-transmitted HEPATITIS C which is associated with transfusions and drug abuse. Hepatitis C virus is the type species.Transcription, Genetic: The biosynthesis of RNA carried out on a template of DNA. The biosynthesis of DNA from an RNA template is called REVERSE TRANSCRIPTION.RNA Replicase: 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)Respiratory Syncytial Viruses: 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.Cricetinae: A subfamily in the family MURIDAE, comprising the hamsters. Four of the more common genera are Cricetus, CRICETULUS; MESOCRICETUS; and PHODOPUS.Orthomyxoviridae Infections: Virus diseases caused by the ORTHOMYXOVIRIDAE.DNA Replication Timing: The temporal order in which the DNA of the GENOME is replicated.Herpesvirus 1, Human: 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.Virulence: 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.Simplexvirus: A genus of the family HERPESVIRIDAE, subfamily ALPHAHERPESVIRINAE, consisting of herpes simplex-like viruses. The type species is HERPESVIRUS 1, HUMAN.Genetic Vectors: 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.Hemagglutinin Glycoproteins, Influenza Virus: 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.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.DNA Helicases: 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.Capsid: The outer protein protective shell of a virus, which protects the viral nucleic acid.HIV Infections: Includes the spectrum of human immunodeficiency virus infections that range from asymptomatic seropositivity, thru AIDS-related complex (ARC), to acquired immunodeficiency syndrome (AIDS).Semliki forest virus: A species of ALPHAVIRUS isolated in central, eastern, and southern Africa.Neutralization Tests: 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).Protein Binding: 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.Transfection: 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.DNA Primers: 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.Parainfluenza Virus 1, Human: A species of RESPIROVIRUS also called hemadsorption virus 2 (HA2), which causes laryngotracheitis in humans, especially children.Nucleic Acid Conformation: The spatial arrangement of the atoms of a nucleic acid or polynucleotide that results in its characteristic 3-dimensional shape.Viral Load: 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.Antibodies, Viral: Immunoglobulins produced in response to VIRAL ANTIGENS.Virus Integration: 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.Viral Core Proteins: Proteins found mainly in icosahedral DNA and RNA viruses. They consist of proteins directly associated with the nucleic acid inside the NUCLEOCAPSID.Capsid Proteins: Proteins that form the CAPSID of VIRUSES.Replication Protein C: 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.HIV: 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.Herpesvirus 4, Human: 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.Tumor Virus Infections: 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.BK Virus: 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.DNA-Directed DNA Polymerase: 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.Escherichia coli: 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.Viral Interference: A phenomenon in which infection by a first virus results in resistance of cells or tissues to infection by a second, unrelated virus.Mosaic Viruses: Viruses which produce a mottled appearance of the leaves of plants.Viral Structural Proteins: 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).Oncogenic Viruses: Viruses that produce tumors.Myxoma virus: The type species of LEPORIPOXVIRUS causing infectious myxomatosis, a severe generalized disease, in rabbits. Tumors are not always present.Mumps virus: The type species of RUBULAVIRUS that causes an acute infectious disease in humans, affecting mainly children. Transmission occurs by droplet infection.Viremia: The presence of viruses in the blood.Polymerase Chain Reaction: 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.Cell Nucleus: 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)Time Factors: Elements of limited time intervals, contributing to particular results or situations.Inclusion Bodies, Viral: 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.Sendai virus: The type species of RESPIROVIRUS in the subfamily PARAMYXOVIRINAE. It is the murine version of HUMAN PARAINFLUENZA VIRUS 1, distinguished by host range.Influenza A virus: The type species of the genus INFLUENZAVIRUS A that causes influenza and other diseases in humans and animals. Antigenic variation occurs frequently between strains, allowing classification into subtypes and variants. Transmission is usually by aerosol (human and most non-aquatic hosts) or waterborne (ducks). Infected birds shed the virus in their saliva, nasal secretions, and feces.Phylogeny: The relationships of groups of organisms as reflected by their genetic makeup.S Phase: 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.Moloney murine leukemia virus: A strain of Murine leukemia virus (LEUKEMIA VIRUS, MURINE) arising during the propagation of S37 mouse sarcoma, and causing lymphoid leukemia in mice. It also infects rats and newborn hamsters. It is apparently transmitted to embryos in utero and to newborns through mother's milk.Gene Products, gag: 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.Virus Attachment: 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.JC 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.Hepatitis A virus: A species in the genus HEPATOVIRUS containing one serotype and two strains: HUMAN HEPATITIS A VIRUS and Simian hepatitis A virus causing hepatitis in humans (HEPATITIS A) and primates, respectively.DNA: 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).Sequence Analysis, DNA: A multistage process that includes cloning, physical mapping, subcloning, determination of the DNA SEQUENCE, and information analysis.Yellow fever virus: The type species of the FLAVIVIRUS genus. Principal vector transmission to humans is by AEDES spp. mosquitoes.Oncolytic Viruses: 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.Simian Acquired Immunodeficiency Syndrome: 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.DucksHaplorhini: 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).Cytomegalovirus: 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.Influenza, Human: An acute viral infection in humans involving the respiratory tract. It is marked by inflammation of the NASAL MUCOSA; the PHARYNX; and conjunctiva, and by headache and severe, often generalized, myalgia.Binding Sites: The parts of a macromolecule that directly participate in its specific combination with another molecule.Avian Sarcoma Viruses: Group of alpharetroviruses (ALPHARETROVIRUS) producing sarcomata and other tumors in chickens and other fowl and also in pigeons, ducks, and RATS.Cowpox virus: A species of ORTHOPOXVIRUS that is the etiologic agent of COWPOX. It is closely related to but antigenically different from VACCINIA VIRUS.Mutagenesis: Process of generating a genetic MUTATION. It may occur spontaneously or be induced by MUTAGENS.Kinetics: The rate dynamics in chemical or physical systems.Tobacco Mosaic Virus: The type species of TOBAMOVIRUS which causes mosaic disease of tobacco. Transmission occurs by mechanical inoculation.Foot-and-Mouth Disease Virus: The type species of APHTHOVIRUS, causing FOOT-AND-MOUTH DISEASE in cloven-hoofed animals. Several different serotypes exist.Gene Deletion: 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.Sequence Deletion: Deletion of sequences of nucleic acids from the genetic material of an individual.RNA, Messenger: 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.Virus Physiological Phenomena: Biological properties, processes, and activities of VIRUSES.Lassa virus: A species of ARENAVIRUS, part of the Old World Arenaviruses (ARENAVIRUSES, OLD WORLD), and the etiologic agent of LASSA FEVER. LASSA VIRUS is a common infective agent in humans in West Africa. Its natural host is the multimammate mouse Mastomys natalensis.Serial Passage: Inoculation of a series of animals or in vitro tissue with an infectious bacterium or virus, as in VIRULENCE studies and the development of vaccines.Species Specificity: 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.Bluetongue virus: The type species of ORBIVIRUS causing a serious disease in sheep, especially lambs. It may also infect wild ruminants and other domestic animals.Proviruses: Duplex DNA sequences in eukaryotic chromosomes, corresponding to the genome of a virus, that are transmitted from one cell generation to the next without causing lysis of the host. Proviruses are often associated with neoplastic cell transformation and are key features of retrovirus biology.Recombinant Proteins: Proteins prepared by recombinant DNA technology.Respiratory Syncytial Virus Infections: Pneumovirus infections caused by the RESPIRATORY SYNCYTIAL VIRUSES. Humans and cattle are most affected but infections in goats and sheep have been reported.Respiratory Syncytial Virus, Human: 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.Chikungunya virus: A species of ALPHAVIRUS causing an acute dengue-like fever.Avian leukosis virus: The type species of ALPHARETROVIRUS producing latent or manifest lymphoid leukosis in fowl.Amino Acid Substitution: 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.Microscopy, Electron: 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.RNA-Directed DNA Polymerase: An enzyme that synthesizes DNA on an RNA template. It is encoded by the pol gene of retroviruses and by certain retrovirus-like elements. EC 2.7.7.49.CD4-Positive T-Lymphocytes: 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.Cell Cycle Proteins: Proteins that control the CELL DIVISION CYCLE. This family of proteins includes a wide variety of classes, including CYCLIN-DEPENDENT KINASES, mitogen-activated kinases, CYCLINS, and PHOSPHOPROTEIN PHOSPHATASES as well as their putative substrates such as chromatin-associated proteins, CYTOSKELETAL PROTEINS, and TRANSCRIPTION FACTORS.Interferon-beta: One of the type I interferons produced by fibroblasts in response to stimulation by live or inactivated virus or by double-stranded RNA. It is a cytokine with antiviral, antiproliferative, and immunomodulating activity.DNA, Single-Stranded: A single chain of deoxyribonucleotides that occurs in some bacteria and viruses. It usually exists as a covalently closed circle.Cell Transformation, Viral: 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.Parainfluenza Virus 3, Human: A species of RESPIROVIRUS frequently isolated from small children with pharyngitis, bronchitis, and pneumonia.Mutagenesis, Site-Directed: Genetically engineered MUTAGENESIS at a specific site in the DNA molecule that introduces a base substitution, or an insertion or deletion.Sequence Alignment: 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.Neuraminidase: An enzyme that catalyzes the hydrolysis of alpha-2,3, alpha-2,6-, and alpha-2,8-glycosidic linkages (at a decreasing rate, respectively) of terminal sialic residues in oligosaccharides, glycoproteins, glycolipids, colominic acid, and synthetic substrate. (From Enzyme Nomenclature, 1992)Encephalitis Viruses, Tick-Borne: A subgroup of the genus FLAVIVIRUS that causes encephalitis and hemorrhagic fevers and is found in eastern and western Europe and the former Soviet Union. It is transmitted by TICKS and there is an associated milk-borne transmission from viremic cattle, goats, and sheep.Hepatitis Delta Virus: A defective virus, containing particles of RNA nucleoprotein in virion-like form, present in patients with acute hepatitis B and chronic hepatitis. It requires the presence of a hepadnavirus for full replication. This is the lone species in the genus Deltavirus.Viruses, Unclassified: Viruses whose taxonomic relationships have not been established.Macrophages: The relatively long-lived phagocytic cell of mammalian tissues that are derived from blood MONOCYTES. Main types are PERITONEAL MACROPHAGES; ALVEOLAR MACROPHAGES; HISTIOCYTES; KUPFFER CELLS of the liver; and OSTEOCLASTS. They may further differentiate within chronic inflammatory lesions to EPITHELIOID CELLS or may fuse to form FOREIGN BODY GIANT CELLS or LANGHANS GIANT CELLS. (from The Dictionary of Cell Biology, Lackie and Dow, 3rd ed.)Porcine respiratory and reproductive syndrome virus: A species of ARTERIVIRUS causing reproductive and respiratory disease in pigs. The European strain is called Lelystad virus. Airborne transmission is common.Protein Biosynthesis: The biosynthesis of PEPTIDES and PROTEINS on RIBOSOMES, directed by MESSENGER RNA, via TRANSFER RNA that is charged with standard proteinogenic AMINO ACIDS.Temperature: 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.Promoter Regions, Genetic: 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.Herpesvirus 3, Human: The type species of VARICELLOVIRUS causing CHICKENPOX (varicella) and HERPES ZOSTER (shingles) in humans.Hepatitis C: INFLAMMATION of the LIVER in humans caused by HEPATITIS C VIRUS, a single-stranded RNA virus. Its incubation period is 30-90 days. Hepatitis C is transmitted primarily by contaminated blood parenterally, and is often associated with transfusion and intravenous drug abuse. However, in a significant number of cases, the source of hepatitis C infection is unknown.Fluorescent Antibody Technique: 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.Vesiculovirus: A genus of the family RHABDOVIRIDAE that infects a wide range of vertebrates and invertebrates. The type species is VESICULAR STOMATITIS INDIANA VIRUS.Trans-Activators: Diffusible gene products that act on homologous or heterologous molecules of viral or cellular DNA to regulate the expression of proteins.Dogs: The domestic dog, Canis familiaris, comprising about 400 breeds, of the carnivore family CANIDAE. They are worldwide in distribution and live in association with people. (Walker's Mammals of the World, 5th ed, p1065)Norwalk virus: The type species in the genus NOROVIRUS, first isolated in 1968 from the stools of school children in Norwalk, Ohio, who were suffering from GASTROENTERITIS. The virions are non-enveloped spherical particles containing a single protein. Multiple strains are named after the places where outbreaks have occurred.Infectious Anemia Virus, Equine: A species of LENTIVIRUS, subgenus equine lentiviruses (LENTIVIRUSES, EQUINE), causing acute and chronic infection in horses. It is transmitted mechanically by biting flies, mosquitoes, and midges, and iatrogenically through unsterilized equipment. Chronic infection often consists of acute episodes with remissions.Reverse Transcriptase Polymerase Chain Reaction: A variation of the PCR technique in which cDNA is made from RNA via reverse transcription. The resultant cDNA is then amplified using standard PCR protocols.Macaca mulatta: 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.Nucleocapsid: A protein-nucleic acid complex which forms part or all of a virion. It consists of a CAPSID plus enclosed nucleic acid. Depending on the virus, the nucleocapsid may correspond to a naked core or be surrounded by a membranous envelope.Enterovirus B, Human: A species of ENTEROVIRUS infecting humans and containing 36 serotypes. It is comprised of all the echoviruses and a few coxsackieviruses, including all of those previously named coxsackievirus B.RNA Virus InfectionsHemagglutinins, Viral: Specific hemagglutinin subtypes encoded by VIRUSES.Retroviridae: Family of RNA viruses that infects birds and mammals and encodes the enzyme reverse transcriptase. The family contains seven genera: DELTARETROVIRUS; LENTIVIRUS; RETROVIRUSES TYPE B, MAMMALIAN; ALPHARETROVIRUS; GAMMARETROVIRUS; RETROVIRUSES TYPE D; and SPUMAVIRUS. A key feature of retrovirus biology is the synthesis of a DNA copy of the genome which is integrated into cellular DNA. After integration it is sometimes not expressed but maintained in a latent state (PROVIRUSES).Tobacco: A plant genus of the family SOLANACEAE. Members contain NICOTINE and other biologically active chemicals; its dried leaves are used for SMOKING.Repetitive Sequences, Nucleic Acid: Sequences of DNA or RNA that occur in multiple copies. There are several types: INTERSPERSED REPETITIVE SEQUENCES are copies of transposable elements (DNA TRANSPOSABLE ELEMENTS or RETROELEMENTS) dispersed throughout the genome. TERMINAL REPEAT SEQUENCES flank both ends of another sequence, for example, the long terminal repeats (LTRs) on RETROVIRUSES. Variations may be direct repeats, those occurring in the same direction, or inverted repeats, those opposite to each other in direction. TANDEM REPEAT SEQUENCES are copies which lie adjacent to each other, direct or inverted (INVERTED REPEAT SEQUENCES).Chick Embryo: 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.Adenoviridae: 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.Cell Cycle: The complex series of phenomena, occurring between the end of one CELL DIVISION and the end of the next, by which cellular material is duplicated and then divided between two daughter cells. The cell cycle includes INTERPHASE, which includes G0 PHASE; G1 PHASE; S PHASE; and G2 PHASE, and CELL DIVISION PHASE.Drug Resistance, Viral: The ability of viruses to resist or to become tolerant to chemotherapeutic agents or antiviral agents. This resistance is acquired through gene mutation.Nucleocapsid Proteins: Viral proteins found in either the NUCLEOCAPSID or the viral core (VIRAL CORE PROTEINS).Restriction Mapping: Use of restriction endonucleases to analyze and generate a physical map of genomes, genes, or other segments of DNA.Leukocytes, Mononuclear: Mature LYMPHOCYTES and MONOCYTES transported by the blood to the body's extravascular space. They are morphologically distinguishable from mature granulocytic leukocytes by their large, non-lobed nuclei and lack of coarse, heavily stained cytoplasmic granules.Open Reading Frames: 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).African Swine Fever Virus: The lone species of the genus Asfivirus. It infects domestic and wild pigs, warthogs, and bushpigs. Disease is endemic in domestic swine in many African countries and Sardinia. Soft ticks of the genus Ornithodoros are also infected and act as vectors.Nuclear Proteins: Proteins found in the nucleus of a cell. Do not confuse with NUCLEOPROTEINS which are proteins conjugated with nucleic acids, that are not necessarily present in the nucleus.Interferons: Proteins secreted by vertebrate cells in response to a wide variety of inducers. They confer resistance against many different viruses, inhibit proliferation of normal and malignant cells, impede multiplication of intracellular parasites, enhance macrophage and granulocyte phagocytosis, augment natural killer cell activity, and show several other immunomodulatory functions.DNA Virus InfectionsMyxovirus Resistance Proteins: Interferon-induced DYNAMIN-like GTP-binding proteins localized in the cytoplasm, nuclear pore complex and nucleus. They play a role in antiviral defense and immunity.Ebolavirus: A genus in the family FILOVIRIDAE consisting of several distinct species of Ebolavirus, each containing separate strains. These viruses cause outbreaks of a contagious, hemorrhagic disease (HEMORRHAGIC FEVER, EBOLA) in humans, usually with high mortality.HIV Core Protein p24: 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.Chickens: Common name for the species Gallus gallus, the domestic fowl, in the family Phasianidae, order GALLIFORMES. It is descended from the red jungle fowl of SOUTHEAST ASIA.Influenza A Virus, H7N7 Subtype: A subtype of INFLUENZA A VIRUS comprised of the surface proteins hemagglutinin 7 and neuraminidase 7. The H7N7 subtype produced an epidemic in 2003 which was highly pathogenic among domestic birds (POULTRY). Some infections in humans were reported.Interferon Type I: Interferon secreted by leukocytes, fibroblasts, or lymphoblasts in response to viruses or interferon inducers other than mitogens, antigens, or allo-antigens. They include alpha- and beta-interferons (INTERFERON-ALPHA and INTERFERON-BETA).tat Gene Products, Human Immunodeficiency Virus: Proteins encoded by the TAT GENES of the HUMAN IMMUNODEFICIENCY VIRUS.Herpesvirus 1, Suid: A species of VARICELLOVIRUS producing a respiratory infection (PSEUDORABIES) in swine, its natural host. It also produces an usually fatal ENCEPHALOMYELITIS in cattle, sheep, dogs, cats, foxes, and mink.Nucleoproteins: Proteins conjugated with nucleic acids.Retroviridae Infections: Virus diseases caused by the RETROVIRIDAE.Encephalitis Viruses: A collection of single-stranded RNA viruses scattered across the Bunyaviridae, Flaviviridae, and Togaviridae families whose common property is the ability to induce encephalitic conditions in infected hosts.Vaccines, Attenuated: 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.Respirovirus: A genus of the family PARAMYXOVIRIDAE (subfamily PARAMYXOVIRINAE) where all the virions have both HEMAGGLUTININ and NEURAMINIDASE activities and encode a non-structural C protein. SENDAI VIRUS is the type species.Origin Recognition Complex: The origin recognition complex is a multi-subunit DNA-binding protein that initiates DNA REPLICATION in eukaryotes.Hepatitis Viruses: Any of the viruses that cause inflammation of the liver. They include both DNA and RNA viruses as well viruses from humans and animals.

Human topoisomerase I promotes initiation of simian virus 40 DNA replication in vitro. (1/23992)

Addition of purified human topoisomerase I (topo I) to simian virus 40 T antigen-driven in vitro DNA replication reactions performed with topo I-deficient extracts results in a greater than 10-fold stimulation of completed molecules as well as a more than 3-fold enhancement of overall DNA replication. To further characterize this stimulation, we first demonstrate that bovine topo I but not Escherichia coli topo I can also enhance DNA replication. By using several human topo I mutants, we show that a catalytically active form of topo I is required. To delineate whether topo I influences the initiation or the elongation step of replication, we performed delayed pulse, pulse-chase, and delayed pulse-chase experiments. The results illustrate that topo I cannot promote the completion of partially replicated molecules but is needed from the beginning of the reaction to initiate replication. Competitive inhibition experiments with the topo I binding T antigen fragment 1-246T and a catalytically inactive topo I mutant suggest that part of topo I's stimulation of replication is mediated through a direct interaction with T antigen. Collectively, our data indicate that topo I enhances the synthesis of fully replicated DNA molecules by forming essential interactions with T antigen and stimulating initiation.  (+info)

High level inhibition of HIV replication with combination RNA decoys expressed from an HIV-Tat inducible vector. (2/23992)

Intracellular immunization, an antiviral gene therapy approach based on the introduction of DNA into cells to stably express molecules for the inhibition of viral gene expression and replication, has been suggested for inhibition of HIV infection. Since the Tat and Rev proteins play a critical role in HIV regulation, RNA decoys and ribozymes of these sequences have potential as therapeutic molecular inhibitors. In the present study, we have generated several anti-HIV molecules; a tat-ribozyme, RRE, RWZ6 and TAR decoys and combinations of decoys, and tested them for inhibition of HIV-1 replication in vitro. We used T cell specific CD2 gene elements and regulatory the HIV inducible promoter to direct high level expression and a 3' UTR sequence for mRNA stabilization. We show that HIV replication was most strongly inhibited with the combination TAR + RRE decoy when compared with the single decoys or the tat-ribozyme. We also show that the Tat-inducible HIV promoter directs a higher level of steady-state transcription of decoys and inhibitors and that higher levels of expression directly relate to increased levels of inhibition of HIV infection. Furthermore, a stabilization of the 3' end of TAR + RRE inhibitor transcripts using a beta-globin 3' UTR sequence leads to an additional 15-fold increase in steady-state RNA levels. This cassette when used to express the best combination decoy inhibitor TAR + RRE, yields high level HIV inhibition for greater than 3 weeks. Taken together, both optimization for high level expression of molecular inhibitors and use of combinations of inhibitors suggest better therapeutic application in limiting the spread of HIV.  (+info)

Enteroviral RNA replication in the myocardium of patients with left ventricular dysfunction and clinically suspected myocarditis. (3/23992)

BACKGROUND: Previous studies dealing with the detection of enteroviral RNA in human endomyocardial biopsies have not differentiated between latent persistence of the enteroviral genome and active viral replication. Enteroviruses that are considered important factors for the development of myocarditis have a single-strand RNA genome of positive polarity that is transcribed by a virus-encoded RNA polymerase into a minus-strand mRNA during active viral replication. The synthesis of multiple copies of minus-strand enteroviral RNA therefore occurs only at sites of active viral replication but not in tissues with mere persistence of the viral genome. METHODS AND RESULTS: We investigated enteroviral RNA replication versus enteroviral RNA persistence in endomyocardial biopsies of 45 patients with left ventricular dysfunction and clinically suspected myocarditis. Using reverse-transcriptase polymerase chain reaction in conjunction with Southern blot hybridization, we established a highly sensitive assay to specifically detect plus-strand versus minus-strand enteroviral RNA in the biopsies. Plus-strand enteroviral RNA was detected in endomyocardial biopsies of 18 (40%) of 45 patients, whereas minus-strand RNA as an indication of active enteroviral RNA replication was detected in only 10 (56%) of these 18 plus-strand-positive patients. Enteroviral RNA was not found in biopsies of the control group (n=26). CONCLUSIONS: These data demonstrate that a significant fraction of patients with left ventricular dysfunction and clinically suspected myocarditis had active enteroviral RNA replication in their myocardium (22%). Differentiation between patients with active viral replication and latent viral persistence should be particularly important in future studies evaluating different therapeutic strategies. In addition, molecular genetic detection of enteroviral genome and differentiation between replicating versus persistent viruses is possible in a single endomyocardial biopsy.  (+info)

Microtubule-dependent plus- and minus end-directed motilities are competing processes for nuclear targeting of adenovirus. (4/23992)

Adenovirus (Ad) enters target cells by receptor-mediated endocytosis, escapes to the cytosol, and then delivers its DNA genome into the nucleus. Here we analyzed the trafficking of fluorophore-tagged viruses in HeLa and TC7 cells by time-lapse microscopy. Our results show that native or taxol-stabilized microtubules (MTs) support alternating minus- and plus end-directed movements of cytosolic virus with elementary speeds up to 2.6 micrometer/s. No directed movement was observed in nocodazole-treated cells. Switching between plus- and minus end-directed elementary speeds at frequencies up to 1 Hz was observed in the periphery and near the MT organizing center (MTOC) after recovery from nocodazole treatment. MT-dependent motilities allowed virus accumulation near the MTOC at population speeds of 1-10 micrometer/min, depending on the cell type. Overexpression of p50/dynamitin, which is known to affect dynein-dependent minus end-directed vesicular transport, significantly reduced the extent and the frequency of minus end-directed migration of cytosolic virus, and increased the frequency, but not the extent of plus end-directed motility. The data imply that a single cytosolic Ad particle engages with two types of MT-dependent motor activities, the minus end- directed cytoplasmic dynein and an unknown plus end- directed activity.  (+info)

Preclinical safety evaluation of human gene therapy products. (5/23992)

Human gene therapy products include naked DNA and viral as well as non-viral vectors containing nucleic acids. There is limited experience on the preclinical toxicity studies necessary for the safety evaluation of these products, which have been outlined in several recently released guidelines. Requirements for the preclinical safety evaluation of human gene therapy products are both specific and non-specific. All key preclinical studies should be performed in compliance with Good Laboratory Practices. Non-specific requirements are in fact common to all pharmaceutical products. Critical specific issues to be addressed are: the safety evaluation of the vector and the toxicity of the expressed protein(s), which are the two components of gene therapy products, the quality of the test article, the selection of animal species, and the verification that the administration method successfully transports the gene of interest, with the vector, to the target site(s). The treatment schedule should mimic the intended human therapeutic design. The host's immune response against the gene therapy product has to be evaluated to detect possible adverse effects and immune neutralization by antibodies. The biodistribution of the gene of interest is also essential and can be evaluated by molecular biology techniques, such as PCR. Specific confinement is required for the safe manipulation of viral vectors.  (+info)

Inhibition of human immunodeficiency virus type 1 replication by combination of transcription inhibitor K-12 and other antiretroviral agents in acutely and chronically infected cells. (6/23992)

8-Difluoromethoxy-1-ethyl-6-fluoro-1,4-dihydro-7-[4-(2-methoxyp hen yl)-1- piperazinyl]-4-oxoquinoline-3-carboxylic acid (K-12) has recently been identified as a potent and selective inhibitor of human immunodeficiency virus type 1 (HIV-1) transcription. In this study, we examined several combinations of K-12 and other antiretroviral agents for their inhibitory effects on HIV-1 replication in acutely and chronically infected cell cultures. Combinations of K-12 and a reverse transcriptase (RT) inhibitor, either zidovudine, lamivudine, or nevirapine, synergistically inhibited HIV-1 replication in acutely infected MT-4 cells. The combination of K-12 and the protease inhibitor nelfinavir (NFV) also synergistically inhibited HIV-1, whereas the synergism of this combination was weaker than that of the combinations with the RT inhibitors. K-12 did not enhance the cytotoxicities of RT and protease inhibitors. Synergism of the combinations was also observed in acutely infected peripheral blood mononuclear cells. The combination of K-12 and cepharanthine, a nuclear factor kappa B inhibitor, synergistically inhibited HIV-1 production in tumor necrosis factor alpha-stimulated U1 cells, a promonocytic cell line chronically infected with the virus. In contrast, additive inhibition was observed for the combination of K-12 and NFV. These results indicate that the combinations of K-12 and clinically available antiretroviral agents may have potential as chemotherapeutic modalities for the treatment of HIV-1 infection.  (+info)

Comparative study of the anti-human cytomegalovirus activities and toxicities of a tetrahydrofuran phosphonate analogue of guanosine and cidofovir. (7/23992)

Cidofovir is the first nucleoside monophosphate analogue currently being used for the treatment of human cytomegalovirus (HCMV) retinitis in individuals with AIDS. Unfortunately, the period of therapy with the use of this compound may be limited due to the possible emergence of serious irreversible nephrotoxic effects. New drugs with improved toxicity profiles are needed. The goal of this study was to investigate the anticytomegaloviral properties and drug-induced toxicity of a novel phosphonate analogue, namely, (-)-2-(R)-dihydroxyphosphinoyl-5-(S)-(guanin-9'-yl-methyl) tetrahydrofuran (compound 1), in comparison with those of cidofovir. The inhibitory activities of both compounds on HCMV propagation in vitro were similar against the AD 169 and Towne strains, with 50% inhibitory concentrations ranging from 0.02 to 0.17 microgram/ml for cidofovir and < 0.05 to 0.09 microgram/ml for compound 1. A clinical HCMV isolate that was resistant to ganciclovir and that had a known mutation within the UL54 DNA polymerase gene and a cidofovir-resistant laboratory strain derived from strain AD 169 remained sensitive to compound 1, whereas their susceptibilities to ganciclovir and cidofovir were reduced by 33- and 10-fold, respectively. Both compound 1 and cidofovir exhibited equal potencies in an experimentally induced murine cytomegalovirus (MCMV) infection in mice, with a prevention or prolongation of mean day to death at dosages of 1.0, 3.2, and 10.0 mg/kg of body weight/day. In cytotoxicity experiments, compound 1 was found to be generally more toxic than cidofovir in cell lines Hs68, HFF, and 3T3-L1 (which are permissive for HCMV or MCMV replication) but less toxic than cidofovir in MRC-5 cells (which are permissive for HCMV replication). Drug-induced toxic side effects were noticed for both compounds in rats and guinea pigs in a 5-day repeated-dose study. In guinea pigs, a greater weight loss was noticed with cidofovir than with compound 1 at dosages of 3.0 and 10.0 mg/kg/day. An opposite effect was detected in rats, which were treated with the compounds at relatively high dosages (up to 100 mg/kg/day). Compound 1 and cidofovir were nephrotoxic in both rats and guinea pigs, with the epithelium lining the proximal convoluted tubules in the renal cortex being the primary target site. The incidence and the severity of the lesions were found to be dose dependent. The lesions observed were characterized by cytoplasm degeneration and nuclear modifications such as karyomegaly, the presence of pseudoinclusions, apoptosis, and degenerative changes. In the guinea pig model, a greater incidence and severity of lesions were observed for cidofovir than for compound 1 (P < 0.001) with a drug regimen of 10 mg/kg/day.  (+info)

Rubella virus-induced apoptosis varies among cell lines and is modulated by Bcl-XL and caspase inhibitors. (8/23992)

Rubella virus (RV) causes multisystem birth defects in the fetuses of infected women. To investigate the cellular basis of this pathology, we examined the cytopathic effect of RV in three permissive cell lines: Vero 76, RK13, and BHK21. Electron microscopy and the TUNEL assay showed that the cytopathic effect resulted from RV-induced programmed cell death (apoptosis) in all three cell lines, but the extent of apoptosis varied among these cells. At 48 h postinfection, the RK13 cell line showed the greatest number of apoptotic cells, the Vero 76 cell line was approximately 3-fold less, and BHK21 had very few. An increased multiplicity of infection and longer time postinfection were required for the BHK21 cell line to reach the level of apoptotic cells in Vero 76 at 48 h. Purified RV induced apoptosis in a dose-dependent fashion, but not UV-inactivated RV or virus-depleted culture supernatant. Specific inhibitors of the apoptosis-specific proteases caspases reduced RV-induced apoptosis and led to higher levels of RV components in infected cells. To address the role of regulatory proteins in RV-induced apoptosis, the antiapoptotic gene Bcl-2 or Bcl-XL was transfected into RK13 cells. Although a high level of Bcl-2 family proteins was expressed, no protection was observed from apoptosis induced by RV, Sindbis virus, or staurosporine in RK13 cells. In BHK21 cells, however, increased expression of Bcl-XL protected cells from apoptosis. The observed variability in apoptotic response to RV of these cell lines demonstrates that programmed cell death is dependent on the unique properties of each cell and may be indicative of how selective organ damage occurs in a congenital rubella syndrome fetus.  (+info)

The regulation of human immunodeficiency virus type 1 infection and replication in primary monocytes was investigated by mutagenesis of recombinant proviral clones containing an env determinant required for the infectivity of monocytes. Virus replication was assayed by determination of reverse transcriptase activity in culture fluids and by recovery of virus from monocytes following cocultivation with uninfected peripheral blood mononuclear cells. Three virus replication phenotypes were observed in monocytes: productive infection, silent infection, and no infection. Incorporation of the monocytetropic env determinant in a full-length clone incapable of infection or replication in primary monocytes (no infection) conferred the capacity for highly efficient virus replication in monocytes (productive infection). Clones with the env determinant but lacking either functional vpr or vpu genes generated lower replication levels in monocytes. Mutation of both vpr and vpu, however, resulted in nearly complete
Using the one-step growth technique the production of the virus T2 in its host, measured by latent period and burst size, was shown to depend on the nutritional environment of the host cell.. When E. coli, grown in broth, was transferred to a simple medium, single organic compounds such as some amino acids and nucleosides were found to increase or accelerate the synthesis of virus.. An antimetabolite of glutamic acid, an amino acid important for virus synthesis, was shown to be inhibitory.. Several naturally occurring amino acids, leucine, serine, and cysteine, inhibited virus synthesis in the simple medium.. A chemically defined mixture was found which supported a rate of virus synthesis very nearly comparable to that found for host cells in nutrient broth.. ...
Yes, this methods works when you know the virus you are incubating and have the right cells available. if you dont know what celltype your virus infects, youll have to try some systems, till you find one that supports virus replication in vitro ...
A single virus particle (virion) cannot replicate or express genetic material (DNA, RNA) without a host cell. Viral infection and virus replication involves six…
To investigate the effect of NP-41V and/or 210D on virus replication, recombinant viruses were generated with reverse-genetics as described previously [21]. For biosafety concerns, the four rescued viruses were performed using G1 (H9N2) backbones: rgG1-WT, rgG1-NP-V41I, rgG1-D210E, and rgG1- NP-V41I-D210E. MDCK cells were infected with rescued viruses at a multiplicity of infection (MOI) of 0.001, and incubated in the appropriate medium containing 2 mg/L N-p-tosyl-L-phenylalaninechloromethyl ketone-treated (TPCK) trypsin (Sigma, Saint Louis, MO, USA) at 33 or 37°C. At 12, 24, 48, 72, and 96 hours post inoculation (hpi), supernatants were harvested and virus titers were determined using MDCK cells, as described previously [22]. As shown in Figure 3B, at 37°C, the D210E substitution in the NP protein significantly decreased the replication ability of rgG1-WT at early stages post infection (12 and 24 hpi (p , 0.05; n = 3), although all four viruses demonstrated comparable growth capability at ...
Endothelial cells are believed to play an important role in response to virus infection. Our previous microarray analysis showed that H9N2 virus infection and inactivated viral particle inoculation increased the expression of interferon-inducible transmembrane protein 1 (IFITM1) in human umbilical vein endothelial cells (HUVECs). In present study, we deeply investigated the expression patterns of IFITM1 and IFITM1-mediated antiviral response induced by H9N2 virus infection and inactivated viral particle inoculation in HUVECs. Epithelial cells that are considered target cells of the influenza virus were selected as a reference control. First, we quantified the expression levels of IFITM1 in HUVECs induced by H9N2 virus infection or viral particle inoculation using quantitative real-time PCR and western blot. Second, we observed whether hemagglutinin or neuraminidase affected IFITM1 expression in HUVECs. Finally, we investigated the effect of induced-IFITM1 on the antiviral state in HUVECs by siRNA and
Mathematicians and scientists from two UK universities have collaborated to shed new light on the process of viral replication during an infection.. Experimentalists from the University of Leeds and mathematicians from the University of York devised a mathematical model that gives new insights into the molecular mechanisms behind virus assembly, helping to explain the efficiency of their operation.. Researchers from the Departments of Mathematics and Biology at the University of York have developed a theoretical basis for the speed and efficiency with which viruses assemble the protective proteins for their genetic information - in this case an RNA molecule - during an infection.. The team incorporated multiple specific contacts between the genomic RNA and the proteins in the containers, along with other details of real virus infections, into a mathematical model that demonstrates how these contacts act collectively to reduce the complexity of virus formation.. They thus solved a longstanding ...
The objective: Binding viruses to designer ViroCatcher cells that cannot support viral replication to diagnose, attenuate, and prevent infection. What we intended to do: (1) Make our designer cell safe, (2) Express specific cell surface receptors and antibodies to catch the virus, (3) Transduce the signal after viruses attached for feedback control, and (4) Remove the viruses along with ViroCatcher itself. Anticipated results: the ViroCatcher is made safe for the bloodstream. When it is injected into the bloodstream, our ViroCatcher passively lies around letting viruses attach to it by using its 4 receptors: CD4 (for HIV), Integrin (for various viruses), Sialic Acid (for Influenza), and Antibodies (for Influenza). After enough viruses attach to it, or after a certain amount of time elapses, it removes itself from the bloodstream by calling macrophages to eat it up. ...
IFITMs are broad antiviral factors that block incoming virions in endosomal vesicles, protecting target cells from infection. In the case of HIV-1, we and others reported the existence of an additional antiviral mechanism through which IFITMs lead to the production of virions of reduced infectivity. However, whether this second mechanism of inhibition is unique to HIV or extends to other viruses is currently unknown. To address this question, we have analyzed the susceptibility of a broad spectrum of viruses to the negative imprinting of the virion particles infectivity by IFITMs. The results we have gathered indicate that this second antiviral property of IFITMs extends well beyond HIV and we were able to identify viruses susceptible to the three IFITMs altogether (HIV-1, SIV, MLV, MPMV, VSV, MeV, EBOV, WNV), as well as viruses that displayed a member-specific susceptibility (EBV, DUGV), or were resistant to all IFITMs (HCV, RVFV, MOPV, AAV). The swapping of genetic elements between resistant ...
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Recent studies have shown that replication of hepatitis C virus (HCV) is dependent on miR-122 expression.[20] miR-122 regulates HCV by binding directly to two adjacent sites close to the 5 end of HCV RNA.[21] Although these experiments were conducted using genotype 1a and 1b HCV RNA, the miR-122 binding sites are highly conserved across different genotypes, and miR-122 is also required for replication of infectious type 2a HCV.[22] As miRNAs generally function to repress gene expression by binding to 3UTR sites, this positive regulation of viral replication via a 5UTR represents a novel function for miR-122. The mechanism of regulation is not yet clear. miR-122 stimulates translation of HCV RNA, but not to a sufficient extent to explain its effects on viral replication, indicating that a second stage of the viral replication cycle must also be regulated.[23][24] HCV RNA synthesis is not affected by miR-122, suggesting that regulation of other processes such as RNA stability may occur.[25][26] ...
In vertebrates, successful host defense against viral infections relies heavily on the early production of IFN-α/β, which promotes an antiviral state in adjacent noninfected cells as well as the activation of antiviral cytotoxic lymphocytes (1). IL-12 and TNF-α are also critical cytokines involved in antiviral defense. IL-12 stimulates the proliferation of T cells as well as the production of IFN-γ by both NK and T cells, whereas TNF-α takes part in the activation of cellular immunity and in the induction of apoptosis of infected cells. Plasmacytoid dendritic cells (pDCs)3 have been shown to be specialized in the production of high levels of IFN-α/β and TNF-α in response to a wide variety of viruses in both humans and mice (2).. The molecular mechanisms promoting the production of cytokines by pDCs in response to most viral infections are independent of productive viral replication within the pDC itself and rely on the detection of viral genomes from engulfed viral particles or apoptotic ...
Viruses need living cells for replication and production of virus progeny. Thus far, antiviral therapy primarily targets viral factors but often induces therapy resistance. New improved therapies attempt to targets cellular factors that are essential for viral replication.
Reproduction in Viruses or Replication of viruses are obligate intracellular parasite. They are reproduced only within a host cell. Viruses lack the enzyme for its replication. After reading this article you will know that how do viruses reproduce and its life cycle.
The genotype and phenotype of HSV2-gD27 are stable when the virus is passaged in human epithelial cells in vitro and during acute infection of mice.. HSV2-gD27 was propagated in B78H1-A10 mouse cells, which express human HVEM but not human nectin-1. HSV2-gD27 was not able to infect B78H1-C10 mouse cells, which express human nectin-1 but not HVEM, since the mutation in gD prevents its interaction with nectin-1 (33). To determine the sensitivity of the assay to detect WT virus mixed with HSV2-gD27, we infected B78H1-C10 cells with 400 PFU of WT virus (titrated in ARPE-19 cells) and 106 PFU of HSV2-gD27 (also titrated in ARPE-19 cells), either together or separately, and assayed the number of plaques on B78H1-C10 cells, which support replication of WT virus but not HSV2-gD27. Coinfection of B78H1-C10 cells with the two viruses resulted in a mean of 6.5 plaques, infection with WT virus alone yielded 5.5 plaques, and infection with HSV2-gD27 yielded no plaques. These data indicate that HSV2-gD27 does ...
PositivelyPositive.ca is designed to create awareness around the many HIV and AIDS issues and promotes messages of positive living with HIV
RNase L is a principle mediator of the innate antiviral response and is thus critically important for human health. Virus replication in higher vertebrates is r...
The search for inhibitors of viral replication is dependent on understanding the events taking place at the molecular level during viral infection. All the essential steps during the viral life cycle...
There are more than 25 drugs to control HIV, yet the virus remains one of the worlds biggest health problems. One of the many challenges with existing therapies is that a dormant version of the virus is always lurking in the background, ready to attack the immune system as soon as treatment is interrupted. _______________________________________…
The reason for using drugs from different families is because there is evidence of cross-resistance. That is, if a strain of HIV can defeat one NNRTI it might show resistance to all NNRTIs. An analogy to delaying resistance by administering three different classes of drugs simultaneously is that most people are capable of bunny hopping up one stair-step. Very few are capable of bunny hopping directly to the third step in one hop. In a similar way, a virus might mutate by random chance to defeat one antiviral mechanism. The chances of a virus simultaneously experiencing three mutations that defeat all three antiviral mechanisms is very, very ...
Hi! I am new around here but wanted to see if anyone else is using IVFAdvantage or Attain? I considered both but went with IVFAdvantage because I like
Plants have evolved very good defenses against viruses over the millennia, and we can take advantage of these natural protections against viruses for ourselves.
Plants have evolved very good defenses against viruses over the millennia, and we can take advantage of these natural protections against viruses for ourselves.
Scientists at the Gladstone Institutes discovered that an enzyme called SMYD2 could be a new therapeutic target for flushing out the HIV that hides in infected individuals. Overcoming this latent virus remains the most significant ...
Viruses are small infectious particles that cannot replicate on their own, but need to infect a cell in order to copy. Viral particles (called virions) consist of a protein envelope and a genetic material inside.
Panda Antivirus has found the following viruses in the message: Server : EXCHANGE02 Sent by : [email protected] Address : [email protected] To : [email protected] Subject : Re: Re: My details Date : 05/09/2003 08:48:07 Sent by You File : details.pif Virus : W32/Sobig.F - Deleted http://www.pandasoftware.com ...
One digit Multiplication Activity 4. Free online multiplication activities to help kids learn the multiplication facts. 1st grade year 1 multiplication.
TY - BOOK. T1 - Viral genome replication. AU - Cameron, Craig Eugene. AU - Raney, Kevin D.. AU - Götte, Matthias. PY - 2009/1/1. Y1 - 2009/1/1. N2 - Provides the first comprehensive review of viral genome replication strategies, emphasizing not only pathways and regulation but also the structure-function, mechanism, and inhibition of proteins and enzymes required for this process Currently, there is no single source that permits comparison of the factors, elements, enzymes and/or mechanisms employed by different classes of viruses for genome replication. As a result, we (and our students) often restrict our focus to our particular system, missing out on the opportunity to define unifying themes in viral genome replication or benefit from the advances in other systems. For example, extraordinary biological and experimental paradigms that have been established over the past five years for the DNA replication systems of bacteriophage T4 and T7 will likely be of great value to anyone interested in ...
In vitro fitness assays are essential tools for determining viral replication fitness for viruses such as HIV-1. Various measurements have been used to extrapolate viral replication fitness, ranging from the number of viral particles per infectious unit, growth rate in cell culture, and relative fitness derived from multiple-cycle growth competition assays. Growth competition assays provide a particularly sensitive measurement of fitness since the viruses are competing for cellular targets under identical growth conditions. There are several experimental factors to consider when conducting growth competition assays, including the multiplicity of infection (MOI), sampling times, and viral detection and fitness calculation methods. Each factor can affect the end result and hence must be considered carefully during the experimental design. The protocol presented here includes steps from constructing a new recombinant HIV-1 clone to performing growth competition assays and analyzing the experimental ...
My research interests are centered on viruses, particularly influenza viruses, which are important human and animal pathogens causing widespread clinical and veterinary disease. My group focuses on the fundamental molecular mechanisms of influenza virus replication, aiming to understand the molecular determinants of host range and virulence of influenza viruses. By gaining further insights into the molecular aspects of influenza virus replication we hope to facilitate the development of novel strategies to combat influenza.. Specifically, we address questions ranging from how the influenza virus RNA polymerase transcribes and replicates the segmented negative-sense viral RNA genome in the nucleus of the infected cell to how the RNA genome is exported from the nucleus and assembles into infectious progeny virus particles. We are also interested in the role of host factors in viral replication as well as in understanding the effects of virus infection on the host cell, the molecular mechanisms of ...
RNA virus replication machineries.(A) RdRps of hepatitis C virus and reovirus. Hepatitis C virus is a (+)RNA virus from the Flaviviridae family, while reovirus
Viral and cellular factors responsible for parvovirus target cell specificity have been examined for two serologically indistinguishable strains of the minute virus of mice which infect mouse cells of dissimilar differentiated phenotype. Both the prototype strain and the immunosuppressive strain grow in and form plaques on monolayers of simian virus 40-transformed human fibroblasts, a finding that has allowed the comparison of several aspects of their virus-host cell interactions. Although closely related by antigenic and genomic criteria, both the prototype strain and the immunosuppressive strain are restricted for lytic growth in each others murine host cell, that is, in T cells and fibroblasts, respectively. The host range of each virus variant appears to be specified by a genetic determinant that is stably inherited in the absence of selection. In the restrictive virus-host interaction lytic growth is limited to a small or, in some cases, undetectable subset of the host cell population, and ...
figure 19.4. Adjunctive treatments of HIV-1 and other neurodegenerative disorders. A number of adjunctive therapies are being developed for treatment of HIV-1-associated cognitive impairments. These are directed at pathogenic mechanisms for disease, including those that affect viral replication, modulate neuroinflammation, interdict cell signaling events that lead to neuronal demise, or affect cell migration into the brain or the viral replication cycle (A). Novel approaches are now under development to harness the hosts own immune system to combat disease. These methodologies currently involve direct immunization strategies and novel nanoparticle delivery systems (B). GA, glatiramer acetate; MDM, monocyte derived macrophages; MP, mononuclear phagocyte; PAF, platelet-activating factor; PPARg, peroxisome proliferator-activated receptor gamma.. multifactorial, in that a complex set of toxic reactions including inflammation, glutamatergic neurotoxicity, increases in iron and nitric oxide, ...
The identification of novel antiretroviral agents is required to provide alternative treatment options for HIV-1-infected patients. The screening of a phenotypic cell-based viral replication assay led to the identification of a novel class of 4,5-dihydro-1H-pyrrolo[3,4-c]pyrazol-6-one (pyrrolopyrazolone) HIV-1 inhibitors, exemplified by two compounds: BI-1 and BI-2. These compounds inhibited early postentry stages of viral replication at a step(s) following reverse transcription but prior to 2 long terminal repeat (2-LTR) circle formation, suggesting that they may block nuclear targeting of the preintegration complex. Selection of viruses resistant to BI-2 revealed that substitutions at residues A105 and T107 within the capsid (CA) amino-terminal domain (CANTD) conferred high-level resistance to both compounds, implicating CA as the antiviral target. Direct binding of BI-1 and/or BI-2 to CANTD was demonstrated using isothermal titration calorimetry and nuclear magnetic resonance (NMR) chemical ...
Inhibition of HIV-1 progeny virion release by cell-surface CD4 is relieved by expression of the viral Nef protein.s profile, publications, research topics, and co-authors
Abstract: A successful infection by a plant virus results from the complex molecular interplay between the host plant and the invading virus. Thus, dissecting the molecular network of virus-host interactions advances the understanding of the viral infection process and may assist in the development of novel antiviral strategies. In the past decade, molecular identification and functional characterization of host factors in the virus life cycle, particularly single-stranded, positive-sense RNA viruses, have been a research focus in plant virology. As a result, a number of host factors have been identified. These host factors are implicated in all the major steps of the infection process. Some host factors are diverted for the viral genome translation, some are recruited to improvise the viral replicase complexes for genome multiplication, and others are components of transport complexes for cell-to-cell spread via plasmodesmata and systemic movement through the phloem. This review summarizes ...
Transcription mapping studies and DNA sequence analysis of the vaccinia virus HindIII D fragment predict that gene D8 encodes a protein 304 amino acids in length, with a molecular mass of 35,426 daltons, that is expressed at late times in infection. In order to determine whether the native D8 protein is required for virus propagation, we constructed a frameshift mutation in the D8 coding sequence. Virus containing this mutation were isolated and shown to replicate in a single-step growth experiment with wild type virus growth kinetics, demonstrating that the normal-length D8 protein is not essential for virus propagation in tissue culture. In order to investigate the synthesis of the wild-type and the mutant D8 proteins in virus-infected cells, we raised polyclonal antisera to a fusion protein consisting of a portion of the D8 coding sequence linked to the Escherichia coli trpE gene. Western blot (immunoblot) analysis of the time course of D8 protein synthesis in cells infected with either ...
Insight on Protein That Blocks HIV Replication May Help Battle Viral Reservoir April 22, 2013 Insight on Protein That Blocks HIV Replication May Help Battle Viral Reservoir Re, team37262board
In Part III of our series on "Strategies for Improving Viral Yield in Vaccine Manufacturing," we will examine the use of manufacturing strategies to improve viral yield and lower cost of production. Improving viral yield and lowering cost is critical for improving access to vaccines in the developing world where even minor medical expenses are prohibitive. Improving viral yield also enables a faster response time in case of a pandemic. Improving cell culture media is one way to increase virus yield and was examined in Part I titled "Improving Media to Increase Virus Yield in Vaccine Production." In Part II titled "Utilizing Bioreactors to Increase Virus Production in Vaccine Manufacturing," we discussed the role of bioreactors and accompanying technology as another way to achieve higher yield. In Part III we will look at additional strategies that can be employed as part of the manufacturing process to achieve higher yield and reduce cost.. In vaccine manufacturing keeping viruses stable during ...
We believe that it is necessary to address each of these problem areas in order to deliver a successful curative combination therapy for HBV. Any such cure needs to rapidly, completely and sustainably reduce HBV viral load to undetectable levels, stimulate and reactivate the patients immune response in order to enable the body to fight HBV, and inhibit the formation of and eliminate viral cccDNA in the infected liver cells.. Aggressive Suppression of HBV Replication. Determining the level of viral replication at the site of infection in the liver is difficult and invasive. Because of this, alternative measurements, which utilize blood as a surrogate, are typically used. This is not ideal, because significantly more virus can be found in the liver than in the bloodstream. Although current HBV therapies do lead to undetectable virus levels in the blood in some infected patients, it is believed that low-level viral replication continues to occur in infected liver cells. The likelihood of ...
English: A simplified diagram of the Hepatitis C virus replication cycle. Created by User:GrahamColm (Photo credit: Wikipedia) ...
In a study published Wednesday in Nature Communications, researchers discovered that certain strains of H7N9 have mutated to become highly resistant to antivirals like Tamiflu while maintaining high levels of pathogenicity. This is not normal. Normally when a virus acquires drug-resistance through mutation, this mutation attenuates it, decreasing viral virulence or replication ability. The study…
A variety of different methods for the evaluation of antiviral agents in cell culture systems are briefly reviewed. It has been repeatedly noted that many test conditions such as the cell culture system, virus strain, virus challenge dose, virus input multiplicity of infection, and time of harvesting, etc., can substantially affect or even alter the test results, thus making comparative studies and unambiguous evaluations very difficult. Attempts are made to discuss previous test methods together with our recent studies with the aim to simplify test procedures and assay methods. Suggestions are proposed for in vitro evaluation of new antiviral agents. It is hoped that this review will alarm investigators to the problems of assaying new antiviral agents. If the suggestions made in this review can be followed, the screening of the enormous number of promising antiviral compounds may be made more efficiently in the near future.
... blue-green alga Spirulina, exhibits activity against a variety of viruses.
Accumulation of viral products such as RNA replication intermediates and viral proteins represents a potential stressor for host cells. Rapidly after detection, host cells respond by implementing multiple appropriated defense mechanisms, including innate immune and stress responses. The strongest response to several forms of stress, including viral infections, is a global reduction of protein synthesis which promotes cellular survival. Translation suppression is induced by the phosphorylation of the alpha subunit of the eukaryotic translation initiation factor-2 (eIF2α), thereby causing stalling of translation initiation and accumulation of stalled pre-initiation complexes in cytosolic stress granules (SGs). Viruses do not package ribosomes and therefore fully rely on the utilization of the host translation machinery to ensure viral protein synthesis, replication and virus progeny production. As a consequence, virus survival depends on the establishment of a delicate and fine-tuned balance ...
Molecular Plant-Microbe Interactions 23:283-293...Ken Komatsu,1 Masayoshi Hashimoto,1 Johji Ozeki,1 Yasuyuki Yamaji,1 Kensaku Maejima,1 Hiroko Senshu,1 Misako Himeno,1 Yukari Okano,1 Satoshi Kagiwada,2 and Shigetou Namba1...
Vaccines have provided considerable success in preventing viral disease, but they have modest or no therapeutic effect for individuals who are already infected. Consequently, our second arm of antiviral defense has been the development and use of antiviral drugs: they can stop an infection once it has started.. However, despite 50 years of research, our arsenal of antiviral drugs is dangerously small. Only about 30 antiviral drugs are available on the US market, most against herpesviruses and HIV-1. There are many reasons for this paucity of antiviral drugs. Compounds interfering with virus growth can adversely affect the host cell, leading to unacceptable toxicity. Many medically important viruses are dangerous, cannot be propagated in the laboratory or tested in animal systems. Another requirement often difficult to fulfill is that the drugs must completely block virus replication. Many acute virus infections are of short duration; by the time the patient feels ill, virus replication is ...
As shown above, early phase II studies strongly suggest that RBV is needed in protease inhibitor drug regimens. Patients who did not receive RBV in the PROVE trials and those with low-dose RBV (400-1000 mg) in the SPRINT-1 trial had increased viral breakthrough, higher relapse and lower SVR. This data strongly indicates that standard-dose RBV is needed to optimize response to these first generation protease inhibitors by reducing the development of resistance/breakthrough. It is also clear that the initial rapid decrease in HCV viral levels with protease combination therapy is because of inhibition of wild type virus that then leads to the uncovering of pre-existing resistant variants. Resistant variants are present in most patients at very low rates (,1%) and are usually detected after near complete suppression of the dominant, wild type virus. The continued replication of these variants can then lead to a virological breakthrough. To date, mutations conferring TVR-resistance have been ...
Viruses are among the simplest biological systems and are highly effective vehicles for the delivery of genetic material into susceptible host cells. Artificial viruses can be used as model systems for providing insights into natural viruses and can be considered a testing ground for developing artificial life. Moreover, they are used in biomedical and biotechnological applications, such as targeted delivery of nucleic acids for gene therapy and as scaffolds in material science. In a natural setting, survival of viruses requires that a significant fraction of the replicated genomes be completely protected by coat proteins. Complete protection of the genome is ensured by a highly cooperative supramolecular process between the coat proteins and the nucleic acids, which is based on reversible, weak and allosteric interactions only. However, incorporating this type of supramolecular cooperativity into artificial viruses remains challenging. Here, we report a rational design for a self-assembling ...
A late protein is a viral protein that is formed after replication of the virus. One example is VP4 from simian virus 40 (SV40 ... "DNA Virus Replication". Daniels R, Sadowicz D, Hebert DN (July 2007). "A very late viral protein triggers the lytic release of ... "Organization of the major and minor capsid proteins in human papillomavirus type 33 virus-like particles". J. Gen. Virol. 76 (9 ...
... virus 3 Acidianus filamentous virus 6 Acidianus filamentous virus 7 Acidianus filamentous virus 8 Acidianus filamentous virus 9 ... Viral replication is cytoplasmic. Entry into the host cell is achieved by adsorption into the host cell. Dna templated ... Betalipothrixvirus is a genus of viruses in the order Ligamenvirales, in the family Lipothrixviridae. Archaea serve as natural ... There are currently six species in this genus including the type species Sulfolobus islandicus filamentous virus. Group: dsDNA ...
The treatment reduces viral replication in the liver, thereby reducing the viral load (the amount of virus particles as ... 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 ... Hepatitis B virus (HBV) is a member of the hepadnavirus family.[36] The virus particle (virion) consists of an outer lipid ...
Viral replication is cytoplasmic. Entry into the host cell is achieved by adsorption into the host cell. DNA-templated ... Viruses in Turriviridae have icosahedral geometries, and T=31 symmetry. The diameter is around 74 nm. Genomes are linear. ... Turriviridae is a family of viruses; it contains only one genus, Alphaturrivirus. The archaea Sulfolobus solfataricus serve as ... "Virus Taxonomy: 2014 Release". Retrieved 13 August 2015. Viralzone: Turriviridae ICTV. ...
Pyrobaculum spherical virus Thermoproteus tenax spherical virus 1 Viruses in Globuloviridae are enveloped, with spherical ... Viral replication is cytoplasmic. Dna templated transcription is the method of transcription. Pyrobaculum and thermoproteus ... "Virus Taxonomy: 2014 Release". Retrieved 15 June 2015. Häring M, Peng X, Brügger K, Rachel R, Stetter KO, Garrett RA, ... Globuloviridae is a family of viruses. Pyrobaculum and thermoproteus archaea serve as natural hosts. There are currently only ...
... presenting the first described case of exaptation of an enzyme for a virus capsid protein function. Viral replication is ... Thermoproteus tenax virus 1 Viruses in Alphalipothrixvirus are enveloped, with rod-shaped geometries. The diameter is around 38 ... "Virus Taxonomy: 2014 Release". Retrieved 12 June 2015. Janekovic, D.; Wunderl, S.; Holz, I.; Zillig, W.; Gierl, A.; Neumann, H ... The TTV1 virion contains four virus-encoded proteins, TP1-4. The proteins do not display any sequence similarity to structural ...
Moradpour, D; Penin, F; Rice, CM (2007). "Replication of hepatitis C virus". Nature Reviews. Microbiology. 5 (6): 453-63. doi: ... Nonstructural protein 5B (NS5B) is a viral protein found in the hepatitis C virus (HCV). It is an RNA polymerase, having the ... De-novo adds necessary primers for initiation of RNA replication. Several drugs either on the market or in various stages of ... O'Farrell, D; Trowbridge, R; Rowlands, D; Jäger, J (2003). "Substrate complexes of hepatitis C virus RNA polymerase (HC-J4): ...
Viral replication[edit]. Transmission electron micrograph of Chikungunya virus particles. The virus consists of four ... It is a member of the Semliki Forest virus complex and is closely related to Ross River virus, O'nyong'nyong virus, and Semliki ... and false positives can occur with infection due to other related viruses, such as o'nyong'nyong virus and Semliki Forest virus ... Chikungunya virus is passed to humans when a bite from an infected mosquito breaks the skin and introduces the virus into the ...
Viral replication is cytoplasmic. DNA-templated transcription is the method of transcription. The virus exits the host cell by ... Mycoplasmatales virus-laidlawii 2 (L2) (tentative) Mycoplasmatales virus-laidlawii 3 (L3) (tentative) Mycoplasmatales virus- ... This family is poorly studied and little is known about these viruses. The family has one genus, Plasmavirus, which has one ... "Virus Taxonomy: 2014 Release". Retrieved 15 June 2015. Büchen-Osmond, C. (Ed) (2003). 00.053. Plasmaviridae. In: ICTVdB-The ...
Replication follows the positive stranded RNA virus replication model. Positive stranded rna virus transcription is the method ... The virus exits the host cell by bacteria lysis. Enterobacteria serve as the natural host. "Viral Zone". ExPASy. Retrieved 15 ... Allolevivirus is a genus of viruses, in the family Leviviridae. Enterobacteria serve as natural hosts. There are currently only ... "Virus Taxonomy: 2014 Release". Retrieved 15 June 2015. Viralzone: Allolevivirus ICTV. ...
Replication follows the negative stranded RNA virus replication model. Negative stranded rna virus transcription, using ... The virus exits the host cell by budding, and tubule-guided viral movement. Plants serve as the natural host. The virus is ... Viral replication is cytoplasmic. Entry into the host cell is achieved by attachment of the viral G glycoproteins to host ... "Virus Taxonomy: 2014 Release". Retrieved 15 June 2015. Afonso, Claudio L.; Amarasinghe, Gaya K.; Bányai, Krisztián; Bào, Yīmíng ...
Replication follows the positive stranded RNA virus replication model. Positive stranded RNA virus transcription is the method ... Group: ssRNA(+) Order: Unassigned Family: Unassigned Genus: Polemovirus Poinsettia latent virus Viruses in Polemovirus are non- ... Viral replication is cytoplasmic, and is lysogenic. Entry into the host cell is achieved by penetration into the host cell. ... The virus exits the host cell by tubule-guided viral movement. Commercial cultivars of euphorbia pulcherrima serve as the ...
Replication follows the negative stranded RNA virus replication model. Negative stranded RNA virus transcription, using ... The virus exits the host cell by nuclear pore export. Horses, sheep, cattle, rodents, birds, and humans serve as the natural ... Viral replication is nuclear. Entry into the host cell is achieved by attachment of the viral GP glycoproteins to host ... Currently, 16 viruses are assigned to eight species included in one genus in this family. Diseases associated with bornaviruses ...
Replication follows the positive stranded RNA virus replication model. Positive stranded RNA virus transcription is the method ... Viral replication is cytoplasmic. Entry into the host cell is achieved by attachment of the virus to host receptors, which ... The virus exits the host cell by lysis, and viroporins. Cattle serve as the natural host. "Viral Zone". ExPASy. Retrieved 13 ... Hunnivirus is a genus of viruses in the order Picornavirales, in the family Picornaviridae. Cattle serve as natural hosts. ...
Replication follows the positive stranded RNA virus replication model. Positive stranded rna virus transcription is the method ... The virus that causes Hepatitis E belongs to the Orthohepevirus genus. Group: ssRNA+ Order: Unassigned Family: Hepeviridae ... This suggests that a recombination event at some point in the past between at least two distinct viruses gave rise to the ... Hepeviridae is a family of viruses. Human, pig, wild boar, sheep, cow, camel, monkey, some rodents, bats and chickens serve as ...
Replication follows the double-stranded RNA virus replication model. Double-stranded RNA virus transcription is the method of ... The virus exits the host cell by cell to cell movement. Fungi serve as the natural host. Hypovirus CHV1 is the only hypovirus ... Hypovirus is a genus of viruses, in the family Hypoviridae. Fungi serve as natural hosts. There are currently four species in ... "Virus Taxonomy: 2014 Release". Retrieved 15 June 2015. Peever, Tobin; Liu, Yir-Chung; Cortese, Paolo; Milgroom, Michael ( ...
Replication follows the DNA strand displacement model. DNA-templated transcription is the method of transcription. The virus ... Camelpox virus Cowpox virus Ectromelia virus Monkeypox virus Raccoonpox virus Skunkpox virus Taterapox virus Vaccinia virus ... 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 ...
Replication follows the positive stranded RNA virus replication model. Positive stranded RNA virus transcription, using the ... Group: ssRNA(+) Order: Unassigned Family: Tombusviridae Genus: Machlomovirus Maize chlorotic mottle virus Viruses in ... "Virus Taxonomy: 2014 Release". Retrieved 15 June 2015. Wu, J. X.; Wang, Q; Liu, H; Qian, Y. J.; Xie, Y; Zhou, X. P. (2013). " ... The virus exits the host cell by tubule-guided viral movement. Plants serve as the natural host. Transmission routes are ...
Viruses. 2 (7): 1458. doi:10.3390/v2071458. PMC 3185713 . PMID 21994690. Goorha, R (1982). "Frog virus 3 DNA replication occurs ... virus Bohle iridovirus Common midwife toad virus Epizootic haematopoietic necrosis virus European catfish virus Frog virus 3 ... Ambystoma tigrinum virus (ATV), Bohle iridovirus (BIV), and frog virus 3). Ranaviruses are large icosahedral DNA viruses ... There are four other genera of viruses within the family Iridoviridae, but Ranavirus is the only one that includes viruses that ...
Yin P, Hong Z, Yang X, Chung RT, Zhang L (Aug 2015). "A role for retromer in hepatitis C virus replication". Cellular and ... Retromer also seems to play a role in Hepatitis C Virus replication.[15] ...
Replication follows the double-stranded RNA virus replication model. Double-stranded rna virus transcription is the method of ... Viruses included in the genus Cystovirus are enveloped, with icosahedral and Spherical geometries, and T=13, T=2 symmetry. The ... Pseudomonas phage φ7, φ8, φ9, φ10, φ11, φ12, and φ13 have been identified and named, but other cystovirus-like viruses have ... In particular, the structural genes of cystoviruses are highly-similar to those used by a number of dsRNA viruses that infect ...
Replication follows the positive stranded RNA virus replication model. Positive stranded RNA virus transcription is the method ... Botrytis virus F Viruses in Gammaflexiviridae are non-enveloped, with flexuous and Filamentous geometries. The diameter is ... "Virus Taxonomy: 2014 Release". Retrieved 15 June 2015. Howitt, R. L.; Beever, R. E.; Pearson, M. N.; Forster, R. L. (2001). " ... "Genome characterization of Botrytis virus F, a flexuous rod-shaped mycovirus resembling plant 'potex-like' viruses". The ...
Replication follows the positive stranded RNA virus replication model. Positive stranded RNA virus transcription is the method ... The virus exits the host cell by cell-to-cell movement. Fungi serve as the natural host. Transmission routes are parental and ... Narnavirus is a genus of viruses, in the family Narnaviridae. Fungi serve as natural hosts. There are currently only two ... "Virus Taxonomy: 2014 Release". Retrieved 15 June 2015. "Viral Zone". ExPASy. Retrieved 15 June 2015. Viralzone: Narnavirus ICTV ...
Replication follows the double-stranded RNA virus replication model. Double-stranded rna virus transcription is the method of ... Group: dsRNA Order: Unassigned Family: Birnaviridae Genus: Blosnavirus Blotched snakehead virus Viruses in Blosnavirus are non- ... Viral replication is cytoplasmic. Entry into the host cell is achieved by penetration into the host cell. ... Blosnavirus is a genus of viruses, in the family Birnaviridae. Blotched snakehead fish serve as natural hosts. There is ...
Moss B (2006). "Poxviridae: the viruses and their replication". In Fields BN, Knipe DM, Howley PM, et al. (eds.). Fields ... Variola virus Smallpox was caused by infection with Variola virus, which belongs to the genus Orthopoxvirus, the family ... While the Dryvax virus was cultured in the skin of calves and freeze-dried, ACAM2000s virus is cultured in kidney epithelial ... During the 19th century, the cowpox virus used for smallpox vaccination was replaced by vaccinia virus. Vaccinia is in the same ...
Bryant M, Ratner L (1990). "Myristoylation-dependent replication and assembly of human immunodeficiency virus 1". Proc. Natl. ... Lee PP, Linial ML (1994). "Efficient particle formation can occur if the matrix domain of human immunodeficiency virus type 1 ... 1990). "Myristoylation of gag proteins of HIV-1 plays an important role in virus assembly". AIDS Res. Hum. Retroviruses. 6 (6 ... Tashiro A, Shoji S, Kubota Y (1990). "Antimyristoylation of the gag proteins in the human immunodeficiency virus-infected cells ...
... Yau, ... Flaviviridae, Flp-In cell line, NS4B, flavivirus, replication compartment, replication vesicles, tick-borne cephalitis virus ... proteins are not part of the virus coat and are thought to participate in the formation of these viral replication compartments ... We propose that the NS proteins drive the remodeling of ER membranes and that viral RNA, RNA replication, viral polymerase, and ...
This Application Note shows how the Dual luciferase assay can help to assess the Replication of the Hepatitis C Virus ... Dual luciferase assay to assess the replication of the hepatitis C virus subgenomic replicon. Sarah Gretton, Mark Harris ... DLRTM assay utilized to monitor early stage replication events of Hepatitis C virus ... allows the study of replication of the virus, without the release of infectious particles and the necessary containment ...
The Polyomavirus family includes two members, BK virus (BKV) and JC virus (JCV), that naturally infect humans. These viruses ... Productive JCV replication was essential for the induction of the antiviral host response. JCV replication at all steps was ... p53 in polyoma virus transformed REF52 cells. Mor, Orna; Read, Moira; Fried, Mike // Oncogene;12/18/97, Vol. 15 Issue 25, p3113 ... Human endothelial cells allow passage of an archetypal BK virus (BKV) strain � a tool for cultivation and functional studies ...
... passage of virus through the cell wall; (2) entry of virus or its nucleic acid into cells and then to replicative sites in ... The processes involved in plant virus replication may include (1) ... The processes involved in plant virus replication may include *(1). passage of virus through the cell wall; ... Stevens W.A. (1983) Plant Virus Replication. In: Virology of Flowering Plants. Tertiary Level Biology. Springer, Boston, MA. * ...
Source=Scaled up from Image:Virus Replication.svg by User:YK Times, who redrew from w:Image:Virusreplication.png using Adobe ... Scaled up from Image:Virus Replication.svg by User:YK Times, who redrew from w:Image:Virusreplication.png using Adobe ... DescriptionVirus Replication large.svg. A diagram of influenza viral cell invasion and replication. ... From Scheme of Influenza A virus replication (NCBI): "A virion attaches to the host cell membrane using Hemagglutinin(HA) and ...
Viruses are obligate intracellular parasites, relying on their host cells to provide the basic machinery to allow them to ... Major cellular structures involved in virus replication. Figure reprinted with permission from Harper DR (2011) Viruses: ... A general guide to viral replication strategies. Figure reprinted with permission from Harper DR (2011) Viruses: Biology, ... Differing effects of virus infections. Figure reprinted from Harper DR (2011) Viruses: Biology, Applications and Control, with ...
Virus replication levels were recorded 12hpi by live microscopy. B. U6A cells or U6A-hSTAT2-FLAG or U6A-mSTAT2-FLAG cells were ... Mouse STAT2 restricts early dengue virus replication.. Ashour J1, Morrison J, Laurent-Rolle M, Belicha-Villanueva A, Plumlee CR ... By using STAT2(-/-) mice, we also demonstrate that mouse STAT2 restricts early dengue virus replication in vivo. These results ... that NS5-mediated IFN antagonism is essential for efficient virus replication. Moreover, we demonstrate that differences in NS5 ...
New improved therapies attempt to targets cellular factors that are essential for viral replication. ... Viruses need living cells for replication and production of virus progeny. Thus far, antiviral therapy primarily targets viral ... Viruses need living cells for replication and production of virus progeny. Thus far, antiviral therapy primarily targets viral ... Essential role of cyclophilin A for hepatitis C virus replication and virus production and possible link to polyprotein ...
The virus enters the cell, replicates its genetic material, assembles new viruses and exits the host cell to find a new host. ... Replication of the influenza virus involves a host cell. ... The replication of influenza virus starts with the virus ... What is the Influenza Virus?. The influenza virus is responsible for the seasonal flu. There are three types of influenza virus ... Replication of Influenza Virus - Endocytosis to Budding. Medical Science / By Vasanth / Laboratory Testing, Identification & ...
Herein, we investigated the effects of meth on influenza A virus replication in human lung epithelial A549 cells. The cells ... However, little is known about whether meth has the ability to enhance influenza A virus replication, thus increasing severity ... Although the underlying mechanism responsible for the action of meth on attenuating virus replication requires further ... Influenza A virus infections frequently cause epidemics and pandemics of respiratory diseases among human populations. ...
Should something go awry however, the virus can cause mononucleosis or cancers of the lymph. The challenge is that its a ... Duke researchers detail how the Epstein-Barr virus manages to persist quietly inside the immune systems B cells in as many as ... Cancer-causing virus masters cells replication, immortality Epstein-Barr virus steers the B-cell to hide in plain sight ... Cancer-causing virus masters cells replication, immortality. Duke University. Journal. eLife. Funder. American Cancer Society ...
... cytoplasmic replication of some DNA viruses occurs in association with modified cellular membranes. We describe how viruses ... Plus-stranded RNA viruses induce membrane proliferations that support the replication of their genomes. Similarly, ... Modification of intracellular membrane structures for virus replication.. Miller S1, Krijnse-Locker J. ... Viruses are intracellular parasites that use the host cell they infect to produce new infectious progeny. Distinct steps of the ...
The research uses pioneering cryo-electron tomography to reveal the complex viral replication process in vivid detail, opening ... imaged molecular structures vital to how a major class of viruses replicates within infected cells. ... The viruses make replication compartments--essentially new organelles--in which the genome replication process takes place. The ... The replication compartments, or spherules, contain strands of RNA, the genetic code of the virus. Its in these spherules that ...
The search for inhibitors of viral replication is dependent on understanding the events taking place at the molecular level ... Human Immunodeficiency Virus Respiratory Syncytial Virus West Nile Virus Severe Acute Respiratory Syndrome Atazanavir ... Lohmann V, Korner F, Koch J, Herian U, Theilmann L, Bartenschlager R (1999) Replication of subgenomic hepatitis C virus RNAs in ... Severson WE, Schmaljohn CS, Javadian A, Jonsson CB (2003) Ribavirin causes error catastrophe during Hantaan virus replication. ...
Hepatitis C Virus (HCV) Induces Formation of Stress Granules Whose Proteins Regulate HCV RNA Replication and Virus Assembly and ... 2008) Autophagic machinery activated by dengue virus enhances virus replication. Virology 374:240-248. ... mouse hepatitis virus and dengue virus) that subvert the autophagy machinery for their replication, co-localize with autophagy ... In Sindbis virus, tobacco mosaic virus, herpes simplex virus type 1 (HSV-1) and several bacterial infections, autophagy may ...
1D and movie S1) (17). Influenza virus is unusual among RNA viruses in that transcription and replication occur within the cell ... Replication of the influenza virus genome is distinct from transcription in that the RNA product is not capped or ... Organization of the Influenza Virus Replication Machinery. By Arne Moeller, Robert N. Kirchdoerfer, Clinton S. Potter, Bridget ... Organization of the Influenza Virus Replication Machinery. By Arne Moeller, Robert N. Kirchdoerfer, Clinton S. Potter, Bridget ...
DNA viruses have evolved very different replication strategies as well as a rich variety of molecular interactions with their ... DNA viruses have evolved very different replication strategies as well as a rich variety of molecular interactions with their ... DNA Plant and Animal Virus Replication. Crisanto Gutierrez, Centro de Biologia Molecular Severo Ochoa, Consejo Superior de ... Gutierrez, Crisanto, and Martinez‐Salas, Encarnacion(Dec 2001) DNA Plant and Animal Virus Replication. In: eLS. John Wiley & ...
... rendering males more vulnerable than females to this virus, according to research published in the February Journal of Virology ... Androgen enhances replication of hepatitis B virus (HBV), ... Androgen enhances replication of hepatitis B virus (HBV), ... Enhancement of hepatitis B virus replication by androgen and its receptor in mice. J. Virol. 86:1904-1910.). ... "Hepatitis B virus is one of the most important human pathogens," says Ou. "Approximately 350 million people worldwide are ...
Replication of hepatitis C virus in cell culture in DOAJ. DOAJ is an online directory that indexes and provides access to ... Replication of hepatitis C virus in cell culture Biopolymers and Cell. 2009;25(1):44-49 DOI 10.7124/bc.0007C9 ... The technique for replicating hepatitis C virus (HCV) in cell culture has been modified and the susceptibility of the cells of ... The highest infection and replication efficacy have been found in cells of rat Gassers ganglion neurinoma. The peculiar ...
We will highlight current research regarding the role of molecular biology of Junín virus in elucidating virus attenuation. We ... that have expanded knowledge about the pathogenesis and viral replication of Junín virus. We will review the pathogenesis of ... The virus is spread through the aerosolization of host rodent excreta and endemic to the humid pampas of Argentina. Recently, ... Junín virus in various animal models and the role of innate and adaptive immunity during infection. ...
The role of CpG dinucleotides in regulating virus replication kinetics. Sir Henry Dale Fellowships Year of award: 2018 ... There are two discrete regions in the genome of influenza A virus (IAV) that have high numbers of CG. These two regions are ... I will identify which proteins of an infected cell interact with these regions and characterise how ZAP affects IAV replication ... The avoidance of CG is mimicked in the genomes of viruses that cause infections because too many CGs activate the immune ...
"The work we are doing will be applicable to all influenza viruses, including influenza A virus subtype H5N1," said VIDO ... the influenza virus hijacks the host animal or humans cellular machinery and forces it to make more copies of the virus. The ... "If the switch is turned on, the pathway enables efficient production of more viruses. But only the NS1 protein can turn on the ... Yan Zhou and her team have discovered how a crucial pathway that supports the influenza A viruss ability to reproduce itself ...
Replication and Maturation of Viruses. Virus-Host Interactions. Opposed to viruses with a plus-strand RNA genome, viruses with ... and Hantaan virus (Bunyaviridae), but also among plant viruses like Tomato spotted wilt virus (TSWV; Tospovirus genus within ... Examples for these viruses can be found among many medically important viruses like Influenza virus (Orthomyxoviridae), Lasse ... Proteins translated from viral transcripts will support the ongoing replication and subsequent virus maturation, ultimately ...
... Conference 7th to 9th February 2018 Barcelona, Catalonia, Spain Website: http ... sciforum.net/conference/Viruses-2018 Contact person: Dr. Lucia Russo This conference will bring together leading virologists ...
Influenza A virus-generated small RNAs regulate the switch from transcription to replication. Jasmine T. Perez, Andrew Varble, ... 1988) Influenza virus RNA replication in vitro: Synthesis of viral template RNAs and virion RNAs in the absence of an added ... 2009) NS2/NEP protein regulates transcription and replication of the influenza virus RNA genome. J Gen Virol 90:1398-1407. ... 2E); these overall levels correlated with the extent of virus replication (Fig. S1A). Furthermore, H1N1 infection of human, ...
  • Strategies of transcriptional genomic organization of different DNA virus families. (els.net)
  • The nonsegmented negative-strand (NNS) RNA virus vesicular stomatitis virus (VSV) is capable of transcribing its genomic RNA initially in the absence of any apparent specialized replication compartment ( 3 ). (asm.org)
  • Rabies virus nucleoprotein (N) plays vital roles in regulation of viral RNA transcription and replication by encapsidation of the nascent genomic RNA. (biomedsearch.com)
  • Zika virus genomic RNA (red stain) in cerebral cortex of an infant (case-patient no. 66, gestational age 26 wk). (cdc.gov)
  • Moreover, we demonstrate that this feature of CPMV can be used to specifically encapsidate custom RNA by placing a sequence of choice between the RNA-2 sequences required for replication.IMPORTANCE The mechanism whereby members of the order Picornavirales specifically package their genomic RNAs is poorly understood. (jic.ac.uk)
  • Very recently, the natural compound silvestrol isolated from the plant Aglaia foveolata was found to have very potent antiviral effects against the (−)-strand RNA-virus Ebola virus as well as against Corona- and Picornaviruses with a (+)-strand RNA-genome. (mdpi.com)
  • Similar structures have been observed in cells infected with related viruses, including rabies virus (RABV [ 4 , 5 ]), Ebola virus ( 6 ), and measles virus ( 7 ). (asm.org)
  • Rapid detection and quantification of RNA of Ebola and Marburg viruses, Lassa virus, Crimean-Congo hemorrhagic fever virus, Rift Valley fever virus, dengue virus, and yellow fever virus by real-time reverse transcription-PCR. (ajtmh.org)
  • Ebola virus (EBOV) is an enveloped negative-sense, single-stranded RNA virus of the filovirus family that causes severe disease in humans. (ovid.com)
  • Highlights An Ebola virus minigenome assay and a novel counterscreen were used to screen a 200,000 compound library. (ovid.com)
  • The screen identified a benzoquinoline scaffold as an inhibitor of Ebola virus RNA synthesis. (ovid.com)
  • In conclusion, our data suggest that RNAi may provide a powerful therapeutic tool, acting both on replication-competent and on replication-incompetent HBV. (natap.org)
  • To by-pass these tissue barriers, we tested if the larger void spaces (poor in IM content) induced by tumor cell apoptosis enhance the distribution of replication-competent herpes simplex virus (HSV) in tumors. (aacrjournals.org)
  • In conclusion TRAIL or paclitaxel plus TRAIL-induced apoptosis enhances the distribution of replication-competent HSV in MDA-MB-435S tumors. (aacrjournals.org)
  • We will also test if apoptosis-induction enhances the therapeutic efficacy of replication-competent HSV. (aacrjournals.org)
  • I thought you might be interested in this item at http://www.worldcat.org/oclc/873640029 Title: Replication competent viruses for cancer therapy : summarizes the molecular principles of modern viral therapy for cancer Author: Pablo Hernáiz Driever Publisher: Basel : Karger, 2001. (worldcat.org)
  • 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. (worldcat.org)
  • The results define a novel genetic and bioinformatics model for introduction and identification of multi-allelic mutations in replication competent viruses that will be powerful tools for testing the effects of decreased fidelity and increased quasispecies diversity on viral replication, pathogenesis, and evolution. (jcvi.org)
  • This defect can be tracked to a delayed maturation of the viral vesicles from the replication incompetent to the competent state. (plantphysiol.org)
  • By using STAT2(-/-) mice, we also demonstrate that mouse STAT2 restricts early dengue virus replication in vivo. (nih.gov)
  • Inhibitions of PKC by a PKC-specific chemical inhibitor or siRNA suppressed NS5 phosphorylation in vivo, increased viral replication and reduced viability of the DENV-infected cells. (sigmaaldrich.com)
  • To understand whether autophagy can indeed enhance HBV replication in vivo , we generated HBV transgenic mice with liver-specific knockout of the Atg5 gene, a gene critical for the initiation of autophagy. (asm.org)
  • Our results thus demonstrate that autophagy is important for HBV replication in vivo and raise the possibility of targeting this pathway to treat HBV patients. (asm.org)
  • However, whether autophagy can indeed enhance HBV replication in vivo remains unclear. (asm.org)
  • To resolve this discrepancy and to understand whether autophagy indeed affects HBV replication in vivo , we decided to use HBV transgenic mice that we previously established in our laboratory for studies. (asm.org)
  • This creates a virus reservoir in contrast to lytic virus replication, which is thought to be restricted to differentiated epithelial cells in vivo. (bloodjournal.org)
  • Tenofovir inhibits the replication of HSV clinical isolates in human embryonic fibroblasts, keratinocytes, and organotypic epithelial 3D-rafts, decreases HSV replication in human lymphoid and cervical tissues ex vivo , and delays HSV-induced lesions and death of topically treated HSV-infected mice. (pubmedcentralcanada.ca)
  • and ectopic expression of a specific srRNA strongly inhibits BKV DNA replication in vivo in human cells. (umsystem.edu)
  • Once bound to the host cell, viruses enter by a range of mechanisms, often involving uptake into vacuoles, although other routes such as fusion with the cell membrane may be used. (els.net)
  • Viruses that require a lipid envelope (enveloped viruses) can acquire this from a range of cellular sources, including the plasma membrane or internal membranes. (els.net)
  • Acquisition of lipid at the plasma membrane allows the virus to exit from the cell by budding. (els.net)
  • Eventually, the virus is encapsulated into a vesicle that detaches from the cell membrane and enters the cytoplasm. (brighthub.com)
  • This causes the virus to push itself toward the membrane of the vesicle until the two merge. (brighthub.com)
  • The various parts of the virus come together at the host's cell membrane. (brighthub.com)
  • As the viruses assemble, they begin to attach to the cell membrane. (brighthub.com)
  • Nonsegmented negative-strand (NNS) RNA viruses, which include some of the most significant human, animal, and plant pathogens extant, form inclusions that are sites of RNA synthesis and are not circumscribed by a membrane. (asm.org)
  • For NNS RNA viruses, the replication compartment is a cytoplasmic inclusion that is not circumscribed by a cellular membrane. (asm.org)
  • To study how TBEV induces membrane remodeling, we developed an inducible stable cell system expressing the TBEV NS polyprotein in the absence of viral RNA replication. (diva-portal.org)
  • When viruses mutate, as they frequently do, thwarting the action of drugs, the mutations typically occur in these sidechains. (news-medical.net)
  • however, some of the mutations found in the clones might be important in conferring higher replication phenotypes. (nih.gov)
  • Mutations at key points on the enzyme have enabled the virus to infect new species in the past. (infectioncontroltoday.com)
  • In the present study, we mutated the serine (S) at position 389 to alanine (A), glycine (G), aspartic acid (D), asparagine (N), glutamic acid (E), and glutamine (Q) and examined the effects of these mutations on rabies virus transcription and replication in the minigenome. (biomedsearch.com)
  • Analysis of complete genome sequences from SARS-ExoN mutant viral clones revealed unique mutation sets in every genome examined from the same round of replication and a total of 100 unique mutations across the genome. (jcvi.org)
  • CTLs from all of these five macaques rapidly selected for escape mutations in Gag, indicating that vaccine-induced CTLs successfully contained replication of the challenge virus. (rupress.org)
  • We also utilized the ΔB1 virus in an experimental evolution assay to perform an unbiased search for suppressor mutations and identify novel pathways involving B1. (unl.edu)
  • Interestingly, our characterization of the adapted viruses reveals that mutations correlating with a loss of function of the vaccinia B12 pseudokinase provide a striking fitness enhancement to this virus. (unl.edu)
  • We have made use of the ability to produce assembled capsids of CPMV in the absence of replication to examine the putative linkage between RNA replication and packaging in the Picornavirales We have created a series of mutant RNA-1 and RNA-2 molecules and have assessed the effect of the mutations on both the replication and packaging of the viral RNAs. (jic.ac.uk)
  • Recently, significant progress has been achieved with the development of new technologies (e.g. reverse genetics) that have expanded knowledge about the pathogenesis and viral replication of Junín virus. (mdpi.com)
  • We will also summarize current knowledge on Junín virus pathogenesis focusing on the recent development of vaccines and potential therapeutics. (mdpi.com)
  • To assess the contribution of CHIKV replication in skeletal muscle cells to pathogenesis, we engineered a CHIKV strain exhibiting restricted replication in these cells via incorporation of target sequences for skeletal muscle cell-specific miR-206. (jci.org)
  • This mixture of birds and mammals, some for which little associated influenza pathogenesis data exists, provided a unique opportunity to study the ecology, host range, and transmission potential of H9N2 virus. (cdc.gov)
  • HBV-specific CD8 + T cells are believed to play a critical role in the control of HBV replication but are also implicated in the pathogenesis of the disease by destruction of infected liver cells ( 1 , 3 , 8 , 9 ). (jimmunol.org)
  • Our study indicates that circulating microbial products can increase viral replication by inducing immune activation and increasing the number of viral target cells, thus demonstrating that immune activation and T cell proliferation are key factors in AIDS pathogenesis. (jimmunol.org)
  • Transfection of HepAD38 cells with either 1.6 or 4 microg/ml siRNA resulted in a profound inhibition (72% and 98%, respectively) of viral replication (as assessed by real-time quantitative PCR). (kuleuven.be)
  • To determine whether an activated innate immune system can also inhibit HBV replication, in this study we activated natural killer T (NKT) cells in the liver of HBV transgenic mice by a single injection of α-galactosylceramide (α-GalCer), a glycolipid antigen presented to Vα14 + NK1.1 + T cells by the nonclassical major histocompatibility complex class I-like molecule CD1d. (rupress.org)
  • By using HLA-A2 matched effector cells (CD8 + T cell line or clone) and target cells supporting full HBV replication, we demonstrate that virus-specific CD8 + T cells can inhibit HBV replication in HBV-producing hepatocytes with minimal cell lysis. (jimmunol.org)
  • However, this concept was challenged by a series of studies in HBV transgenic mice ( 10 , 11 ) and HBV-infected chimpanzees ( 12 , 13 ), which revealed the mechanism of noncytolytic inhibition of HBV replication, i.e., that HBV-specific CD8 + T cells could inhibit HBV replication without lysis of infected hepatocytes. (jimmunol.org)
  • The group studies processes in a strategic way, focusing not on the fine details of a single important virus, but on large principles that apply to the whole class. (eurekalert.org)
  • In this regard, autophagy serves as an innate host defense mechanism, and some viruses and bacteria produce virulence factors that counteract these antimicrobial processes ( 4 - 7 ). (pnas.org)
  • To maximize the yield of cell culture-based processes, high-yield producer cell lines have to be selected, and efficient virus propagation strategies have to be developed. (mpg.de)
  • This difference was exploited to demonstrate, absent manipulation of the viral genome, that NS5-mediated IFN antagonism is essential for efficient virus replication. (nih.gov)
  • 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. (medworm.com)
  • Taken together these results indicate a complex interaction between CHIKV replication and mosquito innate immune responses and demonstrate similarities as well as differences in the control of alphaviruses and other arboviruses by mosquito immune pathways. (nih.gov)
  • On a more positive note, our results suggest that MHC-I-restricted CD8(+) T cells contribute to the protection induced by the live-attenuated SIV vaccine and demonstrate that vaccine-induced CD8(+) T cell responses can control replication of heterologous challenge viruses. (iavi.org)
  • We report here the engineering and recovery of nsp14-ExoN mutant viruses of severe acute respiratory syndrome coronavirus (SARS-CoV) that have stable growth defects and demonstrate a 21-fold increase in mutation frequency during replication in culture. (jcvi.org)
  • The influence of these materials on the ability of vesicular stomatitis virus (VSV) to infect human epitheloid cervical carcinoma (HeLa) cells was examined by two approaches. (biomedsearch.com)
  • An optimized compound, SW456, exhibits broad spectrum activity against filoviruses, vesicular stomatitis virus and Zika virus. (ovid.com)
  • Investigation of the epigenetic regulation of HBV replication may help to discover novel potential therapeutic targets for drug development with the goal to eradicate the HBV cccDNA pool in hepatocytes. (frontiersin.org)
  • Schacker teamed up with Ashley Haase, M.D., Regents' Professor and Head of Microbiology, and Courtney Fletcher, Pharm.D., dean of the College of Pharmacy at the University of Nebraska Medical Center to measure drug levels and find the impact on HIV-1 replication in those tissues. (medicalnewstoday.com)
  • Mavigner M, Zanoni M, Tharp GK, Habib J, Mattingly CR, Lichterfeld M, Nega MT, Vanderford TH, Bosinger SE, Chahroudi A. Pharmacological Modulation of the Wnt/ß-Catenin Pathway Inhibits Proliferation and Promotes Differentiation of Long-Lived Memory CD4+ T Cells in Antiretroviral Therapy-Suppressed Simian Immunodeficiency Virus-Infected Macaques. (harvard.edu)
  • Recently, encouraging AIDS vaccine trials in macaques have implicated cytotoxic T lymphocytes (CTLs) in the control of the simian human immunodeficiency virus SHIV89.6P that induces acute CD4 + T cell depletion. (rupress.org)
  • However, none of these vaccine regimens have been successful in the containment of replication of the pathogenic simian immunodeficiency viruses (SIVs) that induce chronic disease progression. (rupress.org)
  • Then they drilled down still further, discovering elements within the HBV genome which are recognized by the host's activated androgen receptor, which then boosts viral gene expression and replication. (asm.org)
  • Upon activation, these immune cells were shown to produce cytokines, such as IFN-γ and TNF-α, which suppressed HBV gene expression and replication without destroying the infected hepatocytes. (jimmunol.org)
  • This inactivated adenovirus allows us to deliver DNA to target cells without interference from adenovirus gene expression or replication. (uni-muenchen.de)
  • Kasamatsu H and Nakanishi A (1998) How do animal DNA viruses get to the nucleus? (els.net)
  • For Influenza this process occurs in the nucleus whereas for TSWV, and most other segmented (-)RNA viruses this happens in the cytoplasm. (wur.nl)
  • The virus is encoded by eight individual single-stranded segments of RNA with negative polarity that localize to the nucleus upon viral entry ( 1 ). (pnas.org)