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.Leukemia Virus, Murine: Species of GAMMARETROVIRUS, containing many well-defined strains, producing leukemia in mice. Disease is commonly induced by injecting filtrates of propagable tumors into newborn mice.Leukemia, Experimental: Leukemia induced experimentally in animals by exposure to leukemogenic agents, such as VIRUSES; RADIATION; or by TRANSPLANTATION of leukemic tissues.AKR murine leukemia virus: A strain of Murine leukemia virus (LEUKEMIA VIRUS, MURINE) isolated from spontaneous leukemia in AKR strain mice.Friend murine leukemia virus: A strain of Murine leukemia virus (LEUKEMIA VIRUS, MURINE) producing leukemia of the reticulum-cell type with massive infiltration of liver, spleen, and bone marrow. It infects DBA/2 and Swiss mice.Moloney murine sarcoma virus: A replication-defective murine sarcoma virus (SARCOMA VIRUSES, MURINE) isolated from a rhabdomyosarcoma by Moloney in 1966.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 Infections: Virus diseases caused by the RETROVIRIDAE.Abelson murine leukemia virus: A replication-defective strain of Murine leukemia virus (LEUKEMIA VIRUS, MURINE) capable of transforming lymphoid cells and producing a rapidly progressing lymphoid leukemia after superinfection with FRIEND MURINE LEUKEMIA VIRUS; MOLONEY MURINE LEUKEMIA VIRUS; or RAUSCHER VIRUS.DNA, Viral: Deoxyribonucleic acid that makes up the genetic material of 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).Sarcoma Viruses, Murine: A group of replication-defective viruses, in the genus GAMMARETROVIRUS, which are capable of transforming cells, but which replicate and produce tumors only in the presence of Murine leukemia viruses (LEUKEMIA VIRUS, MURINE).Preleukemia: Conditions in which the abnormalities in the peripheral blood or bone marrow represent the early manifestations of acute leukemia, but in which the changes are not of sufficient magnitude or specificity to permit a diagnosis of acute leukemia by the usual clinical criteria.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.Leukemia Virus, Feline: A species of GAMMARETROVIRUS causing leukemia, lymphosarcoma, immune deficiency, or other degenerative diseases in cats. Several cellular oncogenes confer on FeLV the ability to induce sarcomas (see also SARCOMA VIRUSES, FELINE).Genes, Viral: The functional hereditary units of VIRUSES.Cell Line: Established cell cultures that have the potential to propagate indefinitely.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.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.3T3 Cells: Cell lines whose original growing procedure consisted being transferred (T) every 3 days and plated at 300,000 cells per plate (J Cell Biol 17:299-313, 1963). Lines have been developed using several different strains of mice. Tissues are usually fibroblasts derived from mouse embryos but other types and sources have been developed as well. The 3T3 lines are valuable in vitro host systems for oncogenic virus transformation studies, since 3T3 cells possess a high sensitivity to CONTACT INHIBITION.Mink Cell Focus-Inducing Viruses: Strains of MURINE LEUKEMIA VIRUS discovered in 1976 by Hartley, Wolford, Old, and Rowe and so named because the viruses originally isolated had the capacity to transform cell foci in mink cell cultures. MCF viruses are generated by recombination with ecotropic murine leukemia viruses including AKR, Friend, Moloney, and Rauscher, causing ERYTHROLEUKEMIA and severe anemia in mice.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.Base Sequence: The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.Rauscher Virus: A strain of MURINE LEUKEMIA VIRUS associated with mouse tumors similar to those caused by the FRIEND MURINE LEUKEMIA VIRUS. It is a replication-competent murine leukemia virus. It can act as a helper virus when complexing with a defective transforming component, RAUSCHER SPLEEN FOCUS-FORMING VIRUS.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.RNA, Viral: Ribonucleic acid that makes up the genetic material of viruses.Ribonuclease H: A ribonuclease that specifically cleaves the RNA moiety of RNA:DNA hybrids. It has been isolated from a wide variety of prokaryotic and eukaryotic organisms as well as RETROVIRUSES.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).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.Leukemia Virus, Bovine: The type species of DELTARETROVIRUS that causes a form of bovine lymphosarcoma (ENZOOTIC BOVINE LEUKOSIS) or persistent lymphocytosis.Gammaretrovirus: A genus of RETROVIRIDAE comprising endogenous sequences in mammals, related RETICULOENDOTHELIOSIS VIRUSES, AVIAN, and a reptilian virus. Many species contain oncogenes and cause leukemias and sarcomas.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.Genes, gag: DNA sequences that form the coding region for proteins associated with the viral core in retroviruses. gag is short for group-specific antigen.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.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.Gene Products, env: Retroviral proteins, often glycosylated, coded by the envelope (env) gene. They are usually synthesized as protein precursors (POLYPROTEINS) and later cleaved into the final viral envelope glycoproteins by a viral protease.Viral Envelope Proteins: Layers of protein which surround the capsid in animal viruses with tubular nucleocapsids. The envelope consists of an inner layer of lipids and virus specified proteins also called membrane or matrix proteins. The outer layer consists of one or more types of morphological subunits called peplomers which project from the viral envelope; this layer always consists of glycoproteins.Retroviridae Proteins, Oncogenic: Retroviral proteins that have the ability to transform cells. They can induce sarcomas, leukemias, lymphomas, and mammary carcinomas. Not all retroviral proteins are oncogenic.Leukemia: A progressive, malignant disease of the blood-forming organs, characterized by distorted proliferation and development of leukocytes and their precursors in the blood and bone marrow. Leukemias were originally termed acute or chronic based on life expectancy but now are classified according to cellular maturity. Acute leukemias consist of predominately immature cells; chronic leukemias are composed of more mature cells. (From The Merck Manual, 2006)Viral Proteins: Proteins found in any species of virus.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.Integrases: Recombinases that insert exogenous DNA into the host genome. Examples include proteins encoded by the POL GENE of RETROVIRIDAE and also by temperate BACTERIOPHAGES, the best known being BACTERIOPHAGE LAMBDA.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.Mice, Inbred AKRMice, Inbred Strains: Genetically identical individuals developed from brother and sister matings which have been carried out for twenty or more generations, or by parent x offspring matings carried out with certain restrictions. All animals within an inbred strain trace back to a common ancestor in the twentieth generation.Retroviridae Proteins: Proteins from the family Retroviridae. The most frequently encountered member of this family is the Rous sarcoma virus protein.Genes, pol: DNA sequences that form the coding region for retroviral enzymes including reverse transcriptase, protease, and endonuclease/integrase. "pol" is short for polymerase, the enzyme class of reverse transcriptase.Helper Viruses: Viruses which enable defective viruses to replicate or to form a protein coat by complementing the missing gene function of the defective (satellite) virus. Helper and satellite may be of the same or different genus.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.Genes, env: DNA sequences that form the coding region for the viral envelope (env) proteins in retroviruses. The env genes contain a cis-acting RNA target sequence for the rev protein (= GENE PRODUCTS, REV), termed the rev-responsive element (RRE).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.Virus Assembly: The assembly of VIRAL STRUCTURAL PROTEINS and nucleic acid (VIRAL DNA or VIRAL RNA) to form a VIRUS PARTICLE.Nucleic Acid Hybridization: Widely used technique which exploits the ability of complementary sequences in single-stranded DNAs or RNAs to pair with each other to form a double helix. Hybridization can take place between two complimentary DNA sequences, between a single-stranded DNA and a complementary RNA, or between two RNA sequences. The technique is used to detect and isolate specific sequences, measure homology, or define other characteristics of one or both strands. (Kendrew, Encyclopedia of Molecular Biology, 1994, p503)Cloning, Molecular: The insertion of recombinant DNA molecules from prokaryotic and/or eukaryotic sources into a replicating vehicle, such as a plasmid or virus vector, and the introduction of the resultant hybrid molecules into recipient cells without altering the viability of those cells.Thymus Neoplasms: Tumors or cancer of the THYMUS GLAND.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, Recombinant: Biologically active DNA which has been formed by the in vitro joining of segments of DNA from different sources. It includes the recombination joint or edge of a heteroduplex region where two recombining DNA molecules are connected.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.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.Terminal Repeat Sequences: Nucleotide sequences repeated on both the 5' and 3' ends of a sequence under consideration. For example, the hallmarks of a transposon are that it is flanked by inverted repeats on each end and the inverted repeats are flanked by direct repeats. The Delta element of Ty retrotransposons and LTRs (long terminal repeats) are examples of this concept.Lymphoma: A general term for various neoplastic diseases of the lymphoid tissue.Enhancer Elements, Genetic: Cis-acting DNA sequences which can increase transcription of genes. Enhancers can usually function in either orientation and at various distances from a promoter.Transduction, Genetic: The transfer of bacterial DNA by phages from an infected bacterium to another bacterium. This also refers to the transfer of genes into eukaryotic cells by viruses. This naturally occurring process is routinely employed as a GENE TRANSFER TECHNIQUE.Hylobates: A genus of the family HYLOBATIDAE consisting of six species. The members of this genus inhabit rain forests in southeast Asia. They are arboreal and differ from other anthropoids in the great length of their arms and very slender bodies and limbs. Their major means of locomotion is by swinging from branch to branch by their arms. Hylobates means dweller in the trees. Some authors refer to Symphalangus and Nomascus as Hylobates. The six genera include: H. concolor (crested or black gibbon), H. hoolock (Hoolock gibbon), H. klossii (Kloss's gibbon; dwarf siamang), H. lar (common gibbon), H. pileatus (pileated gibbon), and H. syndactylus (siamang). H. lar is also known as H. agilis (lar gibbon), H. moloch (agile gibbon), and H. muelleri (silvery gibbon).Leukemia, Myeloid, Acute: Clonal expansion of myeloid blasts in bone marrow, blood, and other tissue. Myeloid leukemias develop from changes in cells that normally produce NEUTROPHILS; BASOPHILS; EOSINOPHILS; and MONOCYTES.Paralysis: A general term most often used to describe severe or complete loss of muscle strength due to motor system disease from the level of the cerebral cortex to the muscle fiber. This term may also occasionally refer to a loss of sensory function. (From Adams et al., Principles of Neurology, 6th ed, p45)Mink: Carnivores of genus Mustela of the family MUSTELIDAE. The European mink, which has white upper and lower lips, was widely trapped for commercial purposes and is classified as endangered. The American mink, lacking a white upper lip, is farmed commercially.Thymoma: A neoplasm originating from thymic tissue, usually benign, and frequently encapsulated. Although it is occasionally invasive, metastases are extremely rare. It consists of any type of thymic epithelial cell as well as lymphocytes that are usually abundant. Malignant lymphomas that involve the thymus, e.g., lymphosarcoma, Hodgkin's disease (previously termed granulomatous thymoma), should not be regarded as thymoma. (From Stedman, 25th ed)RNA, Transfer, Pro: A transfer RNA which is specific for carrying proline to sites on the ribosomes in preparation for protein synthesis.Leukemia Virus, Gibbon Ape: A species of GAMMARETROVIRUS causing leukemia in the gibbon ape. Natural transmission is by contact.Avian myeloblastosis virus: A species of ALPHARETROVIRUS causing anemia in fowl.Gene Expression Regulation, Viral: Any of the processes by which cytoplasmic factors influence the differential control of gene action in viruses.Lymphoma, T-Cell: A group of heterogeneous lymphoid tumors representing malignant transformations of T-lymphocytes.DNA Restriction Enzymes: Enzymes that are part of the restriction-modification systems. They catalyze the endonucleolytic cleavage of DNA sequences which lack the species-specific methylation pattern in the host cell's DNA. Cleavage yields random or specific double-stranded fragments with terminal 5'-phosphates. The function of restriction enzymes is to destroy any foreign DNA that invades the host cell. Most have been studied in bacterial systems, but a few have been found in eukaryotic organisms. They are also used as tools for the systematic dissection and mapping of chromosomes, in the determination of base sequences of DNAs, and have made it possible to splice and recombine genes from one organism into the genome of another. EC 3.21.1.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.Proto-Oncogene Proteins c-pim-1: Serine-threonine protein kinases that relay signals from CYTOKINE RECEPTORS and are involved in control of CELL GROWTH PROCESSES; CELL DIFFERENTIATION; and APOPTOSIS.Cell Transformation, Neoplastic: Cell changes manifested by escape from control mechanisms, increased growth potential, alterations in the cell surface, karyotypic abnormalities, morphological and biochemical deviations from the norm, and other attributes conferring the ability to invade, metastasize, and kill.Blotting, Southern: A method (first developed by E.M. Southern) for detection of DNA that has been electrophoretically separated and immobilized by blotting on nitrocellulose or other type of paper or nylon membrane followed by hybridization with labeled NUCLEIC ACID PROBES.Oncogenes: Genes whose gain-of-function alterations lead to NEOPLASTIC CELL TRANSFORMATION. They include, for example, genes for activators or stimulators of CELL PROLIFERATION such as growth factors, growth factor receptors, protein kinases, signal transducers, nuclear phosphoproteins, and transcription factors. A prefix of "v-" before oncogene symbols indicates oncogenes captured and transmitted by RETROVIRUSES; the prefix "c-" before the gene symbol of an oncogene indicates it is the cellular homolog (PROTO-ONCOGENES) of a v-oncogene.Human T-lymphotropic virus 1: A strain of PRIMATE T-LYMPHOTROPIC VIRUS 1 isolated from mature T4 cells in patients with T-lymphoproliferation malignancies. It causes adult T-cell leukemia (LEUKEMIA-LYMPHOMA, T-CELL, ACUTE, HTLV-I-ASSOCIATED), T-cell lymphoma (LYMPHOMA, T-CELL), and is involved in mycosis fungoides, SEZARY SYNDROME and tropical spastic paraparesis (PARAPARESIS, TROPICAL SPASTIC).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.Capsid: The outer protein protective shell of a virus, which protects the viral nucleic acid.Giant Cells: Multinucleated masses produced by the fusion of many cells; often associated with viral infections. In AIDS, they are induced when the envelope glycoprotein of the HIV virus binds to the CD4 antigen of uninfected neighboring T4 cells. The resulting syncytium leads to cell death and thus may account for the cytopathic effect of the virus.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.Genome, Viral: The complete genetic complement contained in a DNA or RNA molecule in a virus.Mice, Inbred BALB CRestriction Mapping: Use of restriction endonucleases to analyze and generate a physical map of genomes, genes, or other segments of DNA.Fusion Proteins, gag-pol: Polyprotein products of a fused portion of retroviral mRNA containing the gag and pol genes. The polyprotein is synthesized only five percent of the time since pol is out of frame with gag, and is generated by ribosomal frameshifting.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.DNA Nucleotidyltransferases: Enzymes that catalyze the incorporation of deoxyribonucleotides into a chain of DNA. EC 2.7.7.-.NIH 3T3 Cells: A continuous cell line of high contact-inhibition established from NIH Swiss mouse embryo cultures. The cells are useful for DNA transfection and transformation studies. (From ATCC [Internet]. Virginia: American Type Culture Collection; c2002 [cited 2002 Sept 26]. Available from 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.Chimera: An individual that contains cell populations derived from different zygotes.Virus Cultivation: Process of growing viruses in live animals, plants, or cultured cells.Proto-Oncogenes: Normal cellular genes homologous to viral oncogenes. The products of proto-oncogenes are important regulators of biological processes and appear to be involved in the events that serve to maintain the ordered procession through the cell cycle. Proto-oncogenes have names of the form c-onc.Antigens, Viral: Substances elaborated by viruses that have antigenic activity.Leukemia, Erythroblastic, Acute: A myeloproliferative disorder characterized by neoplastic proliferation of erythroblastic and myeloblastic elements with atypical erythroblasts and myeloblasts in the peripheral blood.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.Templates, Genetic: Macromolecular molds for the synthesis of complementary macromolecules, as in DNA REPLICATION; GENETIC TRANSCRIPTION of DNA to RNA, and GENETIC TRANSLATION of RNA into POLYPEPTIDES.Binding Sites: The parts of a macromolecule that directly participate in its specific combination with another molecule.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.RNA Viruses: Viruses whose genetic material is RNA.T-Lymphocytes: Lymphocytes responsible for cell-mediated immunity. Two types have been identified - cytotoxic (T-LYMPHOCYTES, CYTOTOXIC) and helper T-lymphocytes (T-LYMPHOCYTES, HELPER-INDUCER). They are formed when lymphocytes circulate through the THYMUS GLAND and differentiate to thymocytes. When exposed to an antigen, they divide rapidly and produce large numbers of new T cells sensitized to that antigen.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.Gene Transfer Techniques: The introduction of functional (usually cloned) GENES into cells. A variety of techniques and naturally occurring processes are used for the gene transfer such as cell hybridization, LIPOSOMES or microcell-mediated gene transfer, ELECTROPORATION, chromosome-mediated gene transfer, TRANSFECTION, and GENETIC TRANSDUCTION. Gene transfer may result in genetically transformed cells and individual organisms.Cell Fusion: Fusion of somatic cells in vitro or in vivo, which results in somatic cell hybridization.Spleen: An encapsulated lymphatic organ through which venous blood filters.Xenotropic murine leukemia virus-related virus: An endogenous GAMMARETROVIRUS from the germ line of mice but isolated from humans. It has close similarity to xenotropic MURINE LEUKEMIA VIRUS.Protein PrecursorsRecombinant Fusion Proteins: Recombinant proteins produced by the GENETIC TRANSLATION of fused genes formed by the combination of NUCLEIC ACID REGULATORY SEQUENCES of one or more genes with the protein coding sequences of one or more genes.Nucleic Acid Conformation: The spatial arrangement of the atoms of a nucleic acid or polynucleotide that results in its characteristic 3-dimensional shape.Oligonucleotides: Polymers made up of a few (2-20) nucleotides. In molecular genetics, they refer to a short sequence synthesized to match a region where a mutation is known to occur, and then used as a probe (OLIGONUCLEOTIDE PROBES). (Dorland, 28th ed)Leukemia, Lymphocytic, Chronic, B-Cell: A chronic leukemia characterized by abnormal B-lymphocytes and often generalized lymphadenopathy. In patients presenting predominately with blood and bone marrow involvement it is called chronic lymphocytic leukemia (CLL); in those predominately with enlarged lymph nodes it is called small lymphocytic lymphoma. These terms represent spectrums of the same disease.Mutagenesis: Process of generating a genetic MUTATION. It may occur spontaneously or be induced by MUTAGENS.Clone Cells: A group of genetically identical cells all descended from a single common ancestral cell by mitosis in eukaryotes or by binary fission in prokaryotes. Clone cells also include populations of recombinant DNA molecules all carrying the same inserted sequence. (From King & Stansfield, Dictionary of Genetics, 4th ed)Leukemia, Lymphoid: Leukemia associated with HYPERPLASIA of the lymphoid tissues and increased numbers of circulating malignant LYMPHOCYTES and lymphoblasts.Muridae: A family of the order Rodentia containing 250 genera including the two genera Mus (MICE) and Rattus (RATS), from which the laboratory inbred strains are developed. The fifteen subfamilies are SIGMODONTINAE (New World mice and rats), CRICETINAE, Spalacinae, Myospalacinae, Lophiomyinae, ARVICOLINAE, Platacanthomyinae, Nesomyinae, Otomyinae, Rhizomyinae, GERBILLINAE, Dendromurinae, Cricetomyinae, MURINAE (Old World mice and rats), and Hydromyinae.Mutagenesis, Insertional: Mutagenesis where the mutation is caused by the introduction of foreign DNA sequences into a gene or extragenic sequence. This may occur spontaneously in vivo or be experimentally induced in vivo or in vitro. Proviral DNA insertions into or adjacent to a cellular proto-oncogene can interrupt GENETIC TRANSLATION of the coding sequences or interfere with recognition of regulatory elements and cause unregulated expression of the proto-oncogene resulting in tumor formation.Cell Line, Transformed: Eukaryotic cell line obtained in a quiescent or stationary phase which undergoes conversion to a state of unregulated growth in culture, resembling an in vitro tumor. It occurs spontaneously or through interaction with viruses, oncogenes, radiation, or drugs/chemicals.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.Molecular Weight: The sum of the weight of all the atoms in a molecule.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.Oncogenic Viruses: Viruses that produce tumors.Lentivirus: A genus of the family RETROVIRIDAE consisting of non-oncogenic retroviruses that produce multi-organ diseases characterized by long incubation periods and persistent infection. Lentiviruses are unique in that they contain open reading frames (ORFs) between the pol and env genes and in the 3' env region. Five serogroups are recognized, reflecting the mammalian hosts with which they are associated. HIV-1 is the type species.Radiation Leukemia Virus: A strain of Murine leukemia virus (LEUKEMIA VIRUS, MURINE) isolated from radiation-induced lymphomas in C57BL mice. It is leukemogenic, thymotrophic, can be transmitted vertically, and replicates only in vivo.Genes: A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms.Animals, Newborn: Refers to animals in the period of time just after birth.Murine Acquired Immunodeficiency Syndrome: Acquired defect of cellular immunity that occurs in mice infected with mouse leukemia viruses (MuLV). The syndrome shows striking similarities with human AIDS and is characterized by lymphadenopathy, profound immunosuppression, enhanced susceptibility to opportunistic infections, and B-cell lymphomas.Gene Products, tax: Transcriptional trans-acting proteins of the promoter elements found in the long terminal repeats (LTR) of HUMAN T-LYMPHOTROPIC VIRUS 1 and HUMAN T-LYMPHOTROPIC VIRUS 2. The tax (trans-activator x; x is undefined) proteins act by binding to enhancer elements in the LTR.Reverse Transcription: The biosynthesis of DNA carried out on a template of RNA.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.Sarcoma, Experimental: Experimentally induced neoplasms of CONNECTIVE TISSUE in animals to provide a model for studying human SARCOMA.Mice, Inbred C57BLGlycoproteins: Conjugated protein-carbohydrate compounds including mucins, mucoid, and amyloid glycoproteins.Tumor Cells, Cultured: Cells grown in vitro from neoplastic tissue. If they can be established as a TUMOR CELL LINE, they can be propagated in cell culture indefinitely.Oligodeoxyribonucleotides: A group of deoxyribonucleotides (up to 12) in which the phosphate residues of each deoxyribonucleotide act as bridges in forming diester linkages between the deoxyribose moieties.Chromosome Deletion: Actual loss of portion of a chromosome.Membrane Fusion: The adherence and merging of cell membranes, intracellular membranes, or artificial membranes to each other or to viruses, parasites, or interstitial particles through a variety of chemical and physical processes.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.Avian Sarcoma Viruses: Group of alpharetroviruses (ALPHARETROVIRUS) producing sarcomata and other tumors in chickens and other fowl and also in pigeons, ducks, and RATS.Hematopoietic Stem Cells: Progenitor cells from which all blood cells derive.Bone Marrow: The soft tissue filling the cavities of bones. Bone marrow exists in two types, yellow and red. Yellow marrow is found in the large cavities of large bones and consists mostly of fat cells and a few primitive blood cells. Red marrow is a hematopoietic tissue and is the site of production of erythrocytes and granular leukocytes. Bone marrow is made up of a framework of connective tissue containing branching fibers with the frame being filled with marrow cells.Recombinant Proteins: Proteins prepared by recombinant DNA technology.Thymus Gland: A single, unpaired primary lymphoid organ situated in the MEDIASTINUM, extending superiorly into the neck to the lower edge of the THYROID GLAND and inferiorly to the fourth costal cartilage. It is necessary for normal development of immunologic function early in life. By puberty, it begins to involute and much of the tissue is replaced by fat.Gene Products, pol: Retroviral proteins coded by the pol gene. They are usually synthesized as a protein precursor (POLYPROTEINS) and later cleaved into final products that include reverse transcriptase, endonuclease/integrase, and viral protease. Sometimes they are synthesized as a gag-pol fusion protein (FUSION PROTEINS, GAG-POL). pol is short for polymerase, the enzyme class of reverse transcriptase.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).Gene Expression Regulation: Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control (induction or repression) of gene action at the level of transcription or translation.Myristic Acids: 14-carbon saturated monocarboxylic acids.Genetic Therapy: Techniques and strategies which include the use of coding sequences and other conventional or radical means to transform or modify cells for the purpose of treating or reversing disease conditions.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.RNA, Transfer: The small RNA molecules, 73-80 nucleotides long, that function during translation (TRANSLATION, GENETIC) to align AMINO ACIDS at the RIBOSOMES in a sequence determined by the mRNA (RNA, MESSENGER). There are about 30 different transfer RNAs. Each recognizes a specific CODON set on the mRNA through its own ANTICODON and as aminoacyl tRNAs (RNA, TRANSFER, AMINO ACYL), each carries a specific amino acid to the ribosome to add to the elongating peptide chains.Protein Processing, Post-Translational: Any of various enzymatically catalyzed post-translational modifications of PEPTIDES or PROTEINS in the cell of origin. These modifications include carboxylation; HYDROXYLATION; ACETYLATION; PHOSPHORYLATION; METHYLATION; GLYCOSYLATION; ubiquitination; oxidation; proteolysis; and crosslinking and result in changes in molecular weight and electrophoretic motility.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.Cricetinae: A subfamily in the family MURIDAE, comprising the hamsters. Four of the more common genera are Cricetus, CRICETULUS; MESOCRICETUS; and PHODOPUS.Endoribonucleases: A family of enzymes that catalyze the endonucleolytic cleavage of RNA. It includes EC 3.1.26.-, EC 3.1.27.-, EC 3.1.30.-, and EC 3.1.31.-.Cats: The domestic cat, Felis catus, of the carnivore family FELIDAE, comprising over 30 different breeds. The domestic cat is descended primarily from the wild cat of Africa and extreme southwestern Asia. Though probably present in towns in Palestine as long ago as 7000 years, actual domestication occurred in Egypt about 4000 years ago. (From Walker's Mammals of the World, 6th ed, p801)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.Teratoma: A true neoplasm composed of a number of different types of tissue, none of which is native to the area in which it occurs. It is composed of tissues that are derived from three germinal layers, the endoderm, mesoderm, and ectoderm. They are classified histologically as mature (benign) or immature (malignant). (From DeVita Jr et al., Cancer: Principles & Practice of Oncology, 3d ed, p1642)Kanamycin Kinase: A class of enzymes that inactivate aminocyclitol-aminoglycoside antibiotics (AMINOGLYCOSIDES) by regiospecific PHOSPHORYLATION of the 3' and/or 5' hydroxyl.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.Mutagenesis, Site-Directed: Genetically engineered MUTAGENESIS at a specific site in the DNA molecule that introduces a base substitution, or an insertion or deletion.DNA, Circular: Any of the covalently closed DNA molecules found in bacteria, many viruses, mitochondria, plastids, and plasmids. Small, polydisperse circular DNA's have also been observed in a number of eukaryotic organisms and are suggested to have homology with chromosomal DNA and the capacity to be inserted into, and excised from, chromosomal DNA. It is a fragment of DNA formed by a process of looping out and deletion, containing a constant region of the mu heavy chain and the 3'-part of the mu switch region. Circular DNA is a normal product of rearrangement among gene segments encoding the variable regions of immunoglobulin light and heavy chains, as well as the T-cell receptor. (Riger et al., Glossary of Genetics, 5th ed & Segen, Dictionary of Modern Medicine, 1992)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.Sequence Homology, Nucleic Acid: The sequential correspondence of nucleotides in one nucleic acid molecule with those of another nucleic acid molecule. Sequence homology is an indication of the genetic relatedness of different organisms and gene function.Oncogene Proteins v-abl: Transforming proteins encoded by the abl oncogenes. Oncogenic transformation of c-abl to v-abl occurs by insertional activation that results in deletions of specific N-terminal amino acids.Leukemia L1210Ribonucleases: Enzymes that catalyze the hydrolysis of ester bonds within RNA. EC 3.1.-.Structure-Activity Relationship: The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups.DNA, Neoplasm: DNA present in neoplastic tissue.Chromosome Mapping: Any method used for determining the location of and relative distances between genes on a chromosome.Enzootic Bovine Leukosis: A lymphoid neoplastic disease in cattle caused by the bovine leukemia virus. Enzootic bovine leukosis may take the form of lymphosarcoma, malignant lymphoma, or leukemia but the presence of malignant cells in the blood is not a consistent finding.Leukemia, Myelogenous, Chronic, BCR-ABL Positive: Clonal hematopoetic disorder caused by an acquired genetic defect in PLURIPOTENT STEM CELLS. It starts in MYELOID CELLS of the bone marrow, invades the blood and then other organs. The condition progresses from a stable, more indolent, chronic phase (LEUKEMIA, MYELOID, CHRONIC PHASE) lasting up to 7 years, to an advanced phase composed of an accelerated phase (LEUKEMIA, MYELOID, ACCELERATED PHASE) and BLAST CRISIS.Zinc Fingers: Motifs in DNA- and RNA-binding proteins whose amino acids are folded into a single structural unit around a zinc atom. In the classic zinc finger, one zinc atom is bound to two cysteines and two histidines. In between the cysteines and histidines are 12 residues which form a DNA binding fingertip. By variations in the composition of the sequences in the fingertip and the number and spacing of tandem repeats of the motif, zinc fingers can form a large number of different sequence specific binding sites.Kinetics: The rate dynamics in chemical or physical systems.Fibroblasts: Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules.Nucleic Acid Heteroduplexes: Double-stranded nucleic acid molecules (DNA-DNA or DNA-RNA) which contain regions of nucleotide mismatches (non-complementary). In vivo, these heteroduplexes can result from mutation or genetic recombination; in vitro, they are formed by nucleic acid hybridization. Electron microscopic analysis of the resulting heteroduplexes facilitates the mapping of regions of base sequence homology of nucleic acids.RNA: A polynucleotide consisting essentially of chains with a repeating backbone of phosphate and ribose units to which nitrogenous bases are attached. RNA is unique among biological macromolecules in that it can encode genetic information, serve as an abundant structural component of cells, and also possesses catalytic activity. (Rieger et al., Glossary of Genetics: Classical and Molecular, 5th ed)Gene Expression: The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.Avian leukosis virus: The type species of ALPHARETROVIRUS producing latent or manifest lymphoid leukosis in fowl.Lymphocytes: White blood cells formed in the body's lymphoid tissue. The nucleus is round or ovoid with coarse, irregularly clumped chromatin while the cytoplasm is typically pale blue with azurophilic (if any) granules. Most lymphocytes can be classified as either T or B (with subpopulations of each), or NATURAL KILLER CELLS.Leukemia, T-Cell: A malignant disease of the T-LYMPHOCYTES in the bone marrow, thymus, and/or blood.Transcription Factors: Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process.Deoxyribonucleotides: A purine or pyrimidine base bonded to a DEOXYRIBOSE containing a bond to a phosphate group.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.Cell-Free System: A fractionated cell extract that maintains a biological function. A subcellular fraction isolated by ultracentrifugation or other separation techniques must first be isolated so that a process can be studied free from all of the complex side reactions that occur in a cell. The cell-free system is therefore widely used in cell biology. (From Alberts et al., Molecular Biology of the Cell, 2d ed, p166)RNA Splicing: The ultimate exclusion of nonsense sequences or intervening sequences (introns) before the final RNA transcript is sent to the cytoplasm.Sodium-Phosphate Cotransporter Proteins, Type III: A family of highly conserved and widely expressed sodium-phosphate cotransporter proteins. They are electrogenic sodium-dependent transporters of phosphate that were originally identified as retroviral receptors in HUMANS and have been described in yeast and many other organisms.Genes, Regulator: Genes which regulate or circumscribe the activity of other genes; specifically, genes which code for PROTEINS or RNAs which have GENE EXPRESSION REGULATION functions.Chloramphenicol O-Acetyltransferase: An enzyme that catalyzes the acetylation of chloramphenicol to yield chloramphenicol 3-acetate. Since chloramphenicol 3-acetate does not bind to bacterial ribosomes and is not an inhibitor of peptidyltransferase, the enzyme is responsible for the naturally occurring chloramphenicol resistance in bacteria. The enzyme, for which variants are known, is found in both gram-negative and gram-positive bacteria. EC, Radiation-Induced: Leukemia produced by exposure to IONIZING RADIATION or NON-IONIZING RADIATION.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.Sequence Deletion: Deletion of sequences of nucleic acids from the genetic material of an individual.Nucleic Acid Denaturation: Disruption of the secondary structure of nucleic acids by heat, extreme pH or chemical treatment. Double strand DNA is "melted" by dissociation of the non-covalent hydrogen bonds and hydrophobic interactions. Denatured DNA appears to be a single-stranded flexible structure. The effects of denaturation on RNA are similar though less pronounced and largely reversible.Codon: A set of three nucleotides in a protein coding sequence that specifies individual amino acids or a termination signal (CODON, TERMINATOR). Most codons are universal, but some organisms do not produce the transfer RNAs (RNA, TRANSFER) complementary to all codons. These codons are referred to as unassigned codons (CODONS, NONSENSE).

Suppression of Moloney sarcoma virus immunity following sensitization with attenuated virus. (1/1467)

Murine sarcoma virus (Moloney strain) (MSV-M)-induced tumors are unusual in that they regularly appear less than 2 weeks after virus inoculation, progress for 1 to 2 weeks, and are rejected by normal adult BALB/c mice. Rejectio leaves the animals immune to tumor induction. In the present study, presensitization of normal adult BALB/c mice with attenuated MSV-M resulted in an altered pattern of tumor immunity. Injection of active MSV-M into the presensitized animals resulted in tumor induction and rejection similar to that observed in normal animals, but rejection failed to produce protection against the secondary inoculation with MSV-M. After the second inoculation with active MSV-M, tumors appeared and progressed but ultimately were rejected. Over 80% of the mice died, 25% after the primary challenge and the remainder after the secondary challenge. At death, all mice had histological evidence of leukemia which was the probable cause of death. The animals that died following the secondary challenge also had evidence of disseminated MSV-M. Solid tumor nodules were found in skeletal muscle distant from the original site of inoculation, and active MSV-M was isolated from spleen and lungs. The possibility that the results were produced by specific suppression of MSV-Moloney leukemia virus immunity is discussed.  (+info)

Inhibition of the rous sarcoma virus long terminal repeat-driven transcription by in vitro methylation: different sensitivity in permissive chicken cells versus mammalian cells. (2/1467)

Rous sarcoma virus (RSV) enhancer sequences in the long terminal repeat (LTR) have previously been shown to be sensitive to CpG methylation. We report further that the high density methylation of the RSV LTR-driven chloramphenicol acetyltransferase reporter is needed for full transcriptional inhibition in chicken embryo fibroblasts and for suppression of tumorigenicity of the RSV proviral DNA in chickens. In nonpermissive mammalian cells, however, the low density methylation is sufficient for full inhibition. The time course of inhibition differs strikingly in avian and mammalian cells: although immediately inhibited in mammalian cells, the methylated RSV LTR-driven reporter is fully inhibited with a significant delay after transfection in avian cells. Moreover, transcriptional inhibition can be overridden by transfection with a high dose of the methylated reporter plasmid in chicken cells but not in hamster cells. The LTR, v-src, LTR proviral DNA is easily capable of inducing sarcomas in chickens but not in hamsters. In contrast, Moloney murine leukemia virus LTR-driven v-src induces sarcomas in hamsters with high incidence. Therefore, the repression of integrated RSV proviruses in rodent cells is directed against the LTR.  (+info)

Gene transfer of cytokine inhibitors into human synovial fibroblasts in the SCID mouse model. (3/1467)

OBJECTIVE: To investigate the effects of retrovirus-based gene delivery of inhibitory cytokines and cytokine inhibitors into human synovial fibroblasts in the SCID mouse model of rheumatoid arthritis (RA). METHODS: The MFG vector was used for gene delivery of tumor necrosis factor alpha receptor (TNFalphaR) p55, viral interleukin-10 (IL-10), and murine IL-10 into RA synovial fibroblasts. The effect on invasion of these cells into human articular cartilage and on perichondrocytic cartilage degradation was examined after 60 days of coimplantation into the SCID mouse. RESULTS: TNFalphaR p55 gene transfer showed only a limited effect on inhibition of RA synovial fibroblast invasiveness and cartilage degradation. In contrast, invasion of the RA synovial fibroblasts into the coimplanted cartilage was strongly inhibited by both viral and murine IL-10. Perichondrocytic cartilage degradation was not affected by either form of IL-10. CONCLUSION: The data show that cytokines can be successfully inserted into the genome of human RA synovial fibroblasts using a retroviral vector delivery system, and that the SCID mouse model of human RA is a valuable tool for examining the effects of gene transfer. In addition, inhibition of more than one cytokine pathway may be required to inhibit both synovial- and chondrocyte-mediated cartilage destruction in RA.  (+info)

Development of viral vectors for gene therapy of beta-chain hemoglobinopathies: optimization of a gamma-globin gene expression cassette. (4/1467)

Progress toward gene therapy of beta-chain hemoglobinopathies has been limited in part by poor expression of globin genes in virus vectors. To derive an optimal expression cassette, we systematically analyzed the sequence requirements and relative strengths of the Agamma- and beta-globin promoters, the activities of various erythroid-specific enhancers, and the importance of flanking and intronic sequences. Expression was analyzed by RNase protection after stable plasmid transfection of the murine erythroleukemia cell line, MEL585. Promoter truncation studies showed that the Agamma-globin promoter could be deleted to -159 without affecting expression, while deleting the beta-globin promoter to -127 actually increased expression compared with longer fragments. Expression from the optimal beta-globin gene promoter was consistently higher than that from the optimal Agamma-globin promoter, regardless of the enhancer used. Enhancers tested included a 2.5-kb composite of the beta-globin locus control region (termed a muLCR), a combination of the HS2 and HS3 core elements of the LCR, and the HS-40 core element of the alpha-globin locus. All three enhancers increased expression from the beta-globin gene to roughly the same extent, while the HS-40 element was notably less effective with the Agamma-globin gene. However, the HS-40 element was able to efficiently enhance expression of a Agamma-globin gene linked to the beta-globin promoter. Inclusion of extended 3' sequences from either the beta-globin or the Agamma-globin genes had no significant effect on expression. A 714-bp internal deletion of Agamma-globin intron 2 unexpectedly increased expression more than twofold. With the combination of a -127 beta-globin promoter, an Agamma-globin gene with the internal deletion of intron 2, and a single copy of the HS-40 enhancer, gamma-globin expression averaged 166% of murine alpha-globin mRNA per copy in six pools and 105% in nine clones. When placed in a retrovirus vector, this cassette was also expressed at high levels in MEL585 cells (averaging 75% of murine alpha-globin mRNA per copy) without reducing virus titers. However, recombined provirus or aberrant splicing was observed in 5 of 12 clones, indicating a significant degree of genetic instability. Taken together, these data demonstrate the development of an optimal expression cassette for gamma-globin capable of efficient expression in a retrovirus vector and form the basis for further refinement of vectors containing this cassette.  (+info)

One-day ex vivo culture allows effective gene transfer into human nonobese diabetic/severe combined immune-deficient repopulating cells using high-titer vesicular stomatitis virus G protein pseudotyped retrovirus. (5/1467)

Retrovirus-mediated gene transfer into long-lived human pluripotent hematopoietic stem cells (HSCs) is a widely sought but elusive goal. A major problem is the quiescent nature of most HSCs, with the perceived requirement for ex vivo prestimulation in cytokines to induce stem cell cycling and allow stable gene integration. However, ex vivo culture may impair stem cell function, and could explain the disappointing clinical results in many current gene transfer trials. To address this possibility, we examined the ex vivo survival of nonobese diabetic/severe combined immune-deficient (NOD/SCID) repopulating cells (SRCs) over 3 days. After 1 day of culture, the SRC number and proliferation declined twofold, and was further reduced by day 3; self-renewal was only detectable in noncultured cells. To determine if the period of ex vivo culture could be shortened, we used a vesicular stomatitis virus G protein (VSV-G) pseudotyped retrovirus vector that was concentrated to high titer. The results showed that gene transfer rates were similar without or with 48 hours prestimulation. Thus, the use of high-titer VSV-G pseudotyped retrovirus may minimize the loss of HSCs during culture, because efficient gene transfer can be obtained without the need for extended ex vivo culture.  (+info)

Gene transfer to human pancreatic endocrine cells using viral vectors. (6/1467)

We have studied the factors that influence the efficiency of infection of human fetal and adult pancreatic endocrine cells with adenovirus, murine retrovirus, and lentivirus vectors all expressing the green fluorescent protein (Ad-GFP, MLV-GFP, and Lenti-GFP, respectively). Adenoviral but not retroviral vectors efficiently infected intact pancreatic islets and fetal islet-like cell clusters (ICCs) in suspension. When islets and ICCs were plated in monolayer culture, infection efficiency with all three viral vectors increased. Ad-GFP infected 90-95% of the cells, whereas infection with MLV-GFP and Lenti-GFP increased only slightly. Both exposure to hepatocyte growth factor/scatter factor (HGF/SF) and dispersion of the cells by removal from the culture dish and replating had substantial positive effects on the efficiency of infection with retroviral vectors. Studies of virus entry and cell replication revealed that cell dispersion and stimulation by HGF/SF may be acting through both mechanisms to increase the efficiency of retrovirus-mediated gene transfer. Although HGF/SF and cell dispersion increased the efficiency of infection with MLV-GFP, only rare cells with weak staining for insulin were infected, whereas approximately 25% of beta-cells were infected with Lenti-GFP. We conclude that adenovirus is the most potent vector for ex vivo overexpression of foreign genes in adult endocrine pancreatic cells and is the best vector for applications where high-level but transient expression is desired. Under the optimal conditions of cell dispersion plus HGF/SF, infection with MLV and lentiviral vectors is reasonably efficient and stable, but only lentiviral vectors efficiently infect pancreatic beta-cells.  (+info)

Transplantation of transduced nonhuman primate CD34+ cells using a gibbon ape leukemia virus vector: restricted expression of the gibbon ape leukemia virus receptor to a subset of CD34+ cells. (7/1467)

The transduction efficiencies of immunoselected rhesus macaque (Macaca mulatta) CD34+ cells and colony-forming progenitor cells based on polymerase chain reaction (PCR) analysis were comparable for an amphotropic Moloney murine leukemia virus (MLV) retroviral vector and a retroviral vector derived from the gibbon ape leukemia virus (GaLV) packaging cell line, PG13. On performing autologous transplantation studies using immunoselected CD34+ cells transduced with the GaLV envelope (env) retroviral vector, less than 1% of peripheral blood (PB) contained provirus. This was true whether bone marrow (BM) or cytokine-mobilized PB immunoselected CD34+ cells were reinfused. This level of marking was evident in two animals whose platelet counts never fell below 50,000/microliter and whose leukocyte counts had recovered by days 8 and 10 after having received 1.7 x 10(7) or greater of cytokine-mobilized CD34+ PB cells/kg. Reverse transcriptase(RT)-PCR analysis of CD34+ subsets for both the GaLV and amphotropic receptor were performed. The expression of the GaLV receptor was determined to be restricted to CD34+ Thy-1+ cells, and both CD34+ CD38+ and CD34+ CD38dim cells, while the amphotropic receptor was present on all CD34+ cell subsets examined. Our findings suggest that, in rhesus macaques, PG13-derived retroviral vectors may only be able to transduce a subset of CD34+ cells as only CD34+ Thy-1+ cells express the GaLV receptor.  (+info)

Retrovirus integration site Mintb encoding the mouse homolog of hnRNP U. (8/1467)

Retroviral genes are not usually expressed in mouse embryonal carcinoma (EC) cells, but they are readily expressed upon differentiation of these cells. We previously reported the isolation of EC cell lines that express a neomycin resistance (neo) gene introduced by a recombinant transducing Moloney murine leukemia virus from specific integration sites, Minta, Mintb, Mintc, or Mintd. In some of these clones, the entire 5' long terminal repeat (LTR) was deleted, and the neo gene was expressed by read-through transcription from upstream cellular promoters in a "promoter-trap" fashion. One such promoter ("promoter B" at the Mintb locus) was found in a CpG island, associated with an upstream enhancer ("enhancer B"). Although enhancer B caused expression of the neo gene in the transductant EC cell line, no endogenous transcription from promoter B was detected in the parental EC or NIH3T3 cells. In contrast, we found a strong counter-flow endogenous transcription unit ("R" for reverse), which apparently interfered with transcription from promoter B. Promoter R turned out to have a bidirectional activity in transfection assays. In normal tissues, promoter R activates gene R, which encodes an 800-residue protein that is highly homologous to the rat and human heterogeneous nuclear ribonucleoprotein U (hnRNP U). Northern and in situ hybridization analyses revealed that gene R was abundantly expressed in the testis, especially in the pachytene spermatocytes and round spermatids.  (+info)

  • We studied this question with the Moloney murine leukemia virus Env, for which activation can be followed by surface (SU)-transmembrane (TM) intersubunit disulfide isomerization and subsequent SU release. (
  • Retrovirus-Based Virus-Like Particle Immunogenicity and Its Modulation by Toll-Like Receptor Activation. (
  • A composition for use in inactivating a proviral DNA integrated into the genome of a host cell latently infected with a retrovirus including isolated nucleic acid sequences comprising a CRISPR-associated endonuclease and a guide RNA, wherein the guide RNA is complementary to a target sequence in a human immunodeficiency virus. (
  • Human immunodeficiency virus (HIV) is an exceptionally deadly retrovirus that has caused more than 20 million deaths over the past two decades. (
  • As HIV uses reverse transcriptase to copy its genetic material and generate new viruses (part of a retrovirus proliferation circle), specific drugs have been designed to disrupt the process and thereby suppress its growth. (
  • The fibroblast line was originally utilized in research focusing on the transformation of the cancer-causing Rous sarcoma virus ( RSV ), but now is popular as a host for acquired immunodeficiency disease ( AIDS ) research, as well as transfection experiments with simian virus 40 ( SV40 ) and recombinant plasmid vectors. (
  • MSV, recombinant virus derived of helper viral and cellular sequences, possesses termini resembling prokaryotic transposable elements. (
  • As part of our ongoing development of RRV Toca 511 in recurrent high-grade glioma, we performed extensive monitoring of the virus in patient tumors and body fluids, including Toca 511 quantitation, integration site identification, and mutation profile characterization. (
  • These studies suggest that retroviral transduction of autoantigen-specific murine CD4 + T cells, using the pGCIRES retroviral vector, may provide a potential method to target and isolate the low frequency of autoantigen-specific murine CD4 + T cells, and provides a rational approach to gene therapy in animal models of autoimmunity. (
  • 1963 and hepatitis A in 1973, but many of the blood varies according to the isolate and genotype of the samples taken for post transfusion illness tested virus from 3008 to 3037 amino acids (6). (
  • This hybrid vector, AdLTR-luc, was created by adding two elements from Moloney murine leukemia virus (MoMLV) flanking the luciferase cDNA into an E1/E3-deleted, replication deficient serotype 5 adenovirus vector (Zheng et al. (
  • Human immunodeficiency virus type 1 and Moloney murine leukemia virus enzymes prefer to cleave the RNA strand one nucleotide away from the RNA-DNA junction. (
  • 2004. NMR structure of the 101-nucleotide core encapsidation signal of the Moloney murine leukemia virus. (
  • AF010170 Plasmid pAMS with hybrid amphotropic/Moloney murine leukemia virus, complete sequence. (
  • Some mutants displayed deletion rates that were lower and others displayed rates that were higher than that of wild-type virus. (
  • Justification: Hepatitis C virus (HCV) continues to be a major disease burden on the world and Man is the only known natural host of Hepatitis C virus (Chivaliez and Pawlotsky, 2007). (
  • Results: of the 259 plasma specimens screened for Hepatitis C virus in this study, 20(7.7%) were positive for anti HCV antibodies by ELISA and 16(6.2%) of the antibodies positive specimen were positive for HCV RNA. (
  • Hepatitis C virus genotype 1b was found in the entire HCV RNA positive sample. (
  • Conclusions: The findings of 6.2% prevalence of HCV infection based on HCV RNA test confirmed that there is Hepatitis C virus in Kaduna State with genotype 1b as the predominant genotype found in all the three senatorial zones. (
  • identified the virus to be Hepatitis C virus (2). (
  • The line exhibits typical epithelial morphology and is susceptible to several viruses including vesicular stomatitis (Indiana and New Jersey strains), infectious bovine rhinotracheitis, and sheep bluetongue virus. (
  • Synthesis of virus-specific RNA, measured by the incorporation of [ 3 H]uridine in the presence of 1 μg/ml actinomycin D, also started at 4 hr pi and its maximum rate occurred between 6 and 8 hr pi. (
  • A phylogenetic tree based on the collection of RT-IN sequences for all retrotranscribing viruses in the NCBI taxonomy and NCBI RefSeq databases. (
  • The NTD is essential for 3' processing and strand transfer, however determining its role in the integration process in lentiviruses and oncogenic viruses has been difficult due to the absence of the full-length structure of IN and the complexity of the protein-protein and protein-DNA interactions involved in the synaptic complex. (
  • The ectodomain of the Ebola virus Gp2 glycoprotein was solubilized with a trimeric, isoleucine zipper derived from GCN4 (pIIGCN4) in place of the hydrophobic fusion peptide at the N terminus. (
  • The filovirus, Ebola virus, has been linked to a number of lethal outbreaks of hemorrhagic fever ( 1 , 2 ). (
  • Here, we report that the intact extracellular part of the Ebola virus subunit Gp2, lacking the N-terminal fusion peptide, can be expressed and solubilized by adding a trimeric zipper in-frame with the predicted coiled-coil region of Gp2. (
  • Most strikingly, electron micrographs (EM) indicate a long rod-shaped structure similar to EM images observed of the low-pH-induced conformation of influenza virus HA2 ( 20 , 21 ) and of fragments of HIV-1 env gp41 ( 22 , 23 ), suggesting a similar role for Ebola Gp2 in membrane fusion. (
  • Enteroviruses of the human enterovirus B species (HEV-Bs) (e.g., coxsackie B viruses [CVBs] and echoviruses) have been implicated as environmental factors that trigger/accelerate type 1 diabetes, but the underlying mechanism remains elusive. (
  • Enteroviruses, particularly human enterovirus B species (HEV-Bs), such as coxsackie B viruses (CVBs) and echoviruses (EVs), are implicated as environmental factors, and a recent meta-analysis confirms that there is a clinically significant association between enterovirus infection and autoimmunity/type 1 diabetes ( 1 ). (
  • This study has adapted the oligonucleotide ligation assay (OLA) to probe for low-level nevirapine (NVP) resistance mutations K103N and Y181C in the human immunodeficiency virus type 1 (HIV-1) population of infected mother-infant pairs from Uganda. (
  • Human immunodeficiency virus type 1 (HIV-1) is the primary etiologic agent for Aquired Immune Deficiency Syndrome (AIDS). (
  • Acquired Immunodeficiency Syndrome (AIDS) and its associated disorders are caused by the human lentivirus, human immunodeficiency virus (HIV-1) (1-6). (
  • We determined whether human papilloma virus (HPV) biomarkers were correlated with anal pathology in these men. (
  • The detection of human papilloma virus (HPV)-related biomarkers in cervical pathology specimens may be helpful in determining the cytologic and histologic diagnostic categories of premalignant and malignant lesions ( 10 - 14 ). (
Sequential activation of the three protomers in the Moloney murine leukemia virus Env | PNAS
Sequential activation of the three protomers in the Moloney murine leukemia virus Env | PNAS (
SWISS-MODEL Template Library | 1d1u.1
SWISS-MODEL Template Library | 1d1u.1 (
Synthesis of Long, Representative DNA Copies of the Murine RNA Tumor Virus Genome | Journal of Virology
Synthesis of Long, Representative DNA Copies of the Murine RNA Tumor Virus Genome | Journal of Virology (
Insulin Deprivation Decreases Caspase-Dependent Apoptotic Signaling in Cultured Rat Sertoli Cells
Insulin Deprivation Decreases Caspase-Dependent Apoptotic Signaling in Cultured Rat Sertoli Cells (
MHC Class I Family Proteins Retard Systemic Lupus Erythematosus Autoimmunity and B Cell Lymphomagenesis | The Journal of...
MHC Class I Family Proteins Retard Systemic Lupus Erythematosus Autoimmunity and B Cell Lymphomagenesis | The Journal of... (
Role of Recycling, Mindbomb1 Association, and Exclusion from Lipid Rafts of Delta-like 4 for Effective Notch Signaling To Drive...
Role of Recycling, Mindbomb1 Association, and Exclusion from Lipid Rafts of Delta-like 4 for Effective Notch Signaling To Drive... (
Cell Motility
Cell Motility (
Targeting Rare Populations of Murine Antigen-Specific T Lymphocytes by Retroviral Transduction for Potential Application in...
Targeting Rare Populations of Murine Antigen-Specific T Lymphocytes by Retroviral Transduction for Potential Application in... (
Distribution of Cycling T Lymphocytes in Blood and Lymphoid Organs During Immune Responses | The Journal of Immunology
Distribution of Cycling T Lymphocytes in Blood and Lymphoid Organs During Immune Responses | The Journal of Immunology (
Pharmacological targets of breast cancer stem cells: a review | SpringerLink
Pharmacological targets of breast cancer stem cells: a review | SpringerLink (
Moloney Murine Leukemia Virus Based Retroviral Vector - Muscular Dystrophy
Moloney Murine Leukemia Virus Based Retroviral Vector - Muscular Dystrophy (
Plus it
Plus it (
Plus it
Plus it (
Production of Pseudotyped Retrovirus and the Generation of Proviral Transgenic Zebrafish | SpringerLink
Production of Pseudotyped Retrovirus and the Generation of Proviral Transgenic Zebrafish | SpringerLink (
Moloney murine leukemia virus integration protein produced in yeast binds specifically to viral att sites. | Journal of Virology
Moloney murine leukemia virus integration protein produced in yeast binds specifically to viral att sites. | Journal of Virology (
Lung CD25 CD4 Regulatory T Cells Suppress Type 2 Immune Responses But Not Bronchial Hyperreactivity | The Journal of Immunology
Lung CD25 CD4 Regulatory T Cells Suppress Type 2 Immune Responses But Not Bronchial Hyperreactivity | The Journal of Immunology (
Plus it
Plus it (
Barrier-to-autointegration factor (BAF) condenses DNA by looping | PNAS
Barrier-to-autointegration factor (BAF) condenses DNA by looping | PNAS (
Administration of α-Galactosylceramide Improves Adenine-Induced Renal Injury | SpringerLink
Administration of α-Galactosylceramide Improves Adenine-Induced Renal Injury | SpringerLink (
Retroviral and Lentiviral Vectors for the Induction of Immunological Tolerance
Retroviral and Lentiviral Vectors for the Induction of Immunological Tolerance (
Isolation and properties of Moloney murine leukemia virus mutants: use of a rapid assay for release of virion reverse...
Isolation and properties of Moloney murine leukemia virus mutants: use of a rapid assay for release of virion reverse... (
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Plus it (
Program in Virology
Program in Virology (
Distinct Morphological Stages of Dentate Granule Neuron Maturation in the Adult Mouse Hippocampus | Journal of Neuroscience
Distinct Morphological Stages of Dentate Granule Neuron Maturation in the Adult Mouse Hippocampus | Journal of Neuroscience (
Sensitive Oligonucleotide Ligation Assay for Low-Level Detection of Nevirapine Resistance Mutations in Human Immunodeficiency...
Sensitive Oligonucleotide Ligation Assay for Low-Level Detection of Nevirapine Resistance Mutations in Human Immunodeficiency... (
CiteSeerX - Citation Query Single-step method of RNA isolation by acid guanidinium thiocyanate-phenolchloroform extraction....
CiteSeerX - Citation Query Single-step method of RNA isolation by acid guanidinium thiocyanate-phenolchloroform extraction.... (
Table of Contents - September 01, 1998, 95 (18) | PNAS
Table of Contents - September 01, 1998, 95 (18) | PNAS (
Milestones Tables : Metrics
Milestones Tables : Metrics (
TGFβ1-induced SMAD2/3 and SMAD1/5 phosphorylation are both ALK5-kinase-dependent in primary chondrocytes and mediated by TAK1...
TGFβ1-induced SMAD2/3 and SMAD1/5 phosphorylation are both ALK5-kinase-dependent in primary chondrocytes and mediated by TAK1... (
Intact Viral Particle Counts Measured by Flow Virometry Provide Insight into the Infectivity and Genome Packaging Efficiency of...
Intact Viral Particle Counts Measured by Flow Virometry Provide Insight into the Infectivity and Genome Packaging Efficiency of... (
Knockdown of Inwardly Rectifying Potassium Channel Kir2.2 Suppresses Tumorigenesis by Inducing Reactive Oxygen Species-Mediated...
Knockdown of Inwardly Rectifying Potassium Channel Kir2.2 Suppresses Tumorigenesis by Inducing Reactive Oxygen Species-Mediated... (
Single-Nucleotide-Specific Targeting of the Tf1 Retrotransposon Promoted by the DNA-Binding Protein Sap1 of Schizosaccharomyces...
Single-Nucleotide-Specific Targeting of the Tf1 Retrotransposon Promoted by the DNA-Binding Protein Sap1 of Schizosaccharomyces... (
Proteins and Peptides
Proteins and Peptides (