Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:2.7.7.49 (reverse transcriptase)
31,746 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Zidovudine is a potent in vitro inhibitor of human immunodeficiency virus (HIV) with varying efficacy against other retroviruses. With the exception of Epstein-Barr virus, all non-retroviruses tested so far have been insensitive to inhibition by zidovudine. In vivo, efficacy of zidovudine was demonstrated against Rauscher murine leukemia virus and feline leukemia virus. In both experimental models, infections completely resolved in animals when the drug was administered soon after infection. These results suggest that prompt initiation of zidovudine therapy, following a known exposure to HIV, should be considered. Mechanism studies show that zidovudine is phosphorylated to the monophosphate and diphosphate derivatives by the host cell cytosolic thymidine kinase and thymidylate kinase, respectively. The identity of the enzyme that phosphorylates zidovudine diphosphate is not known, but is believed to be the cellular nucleoside diphosphate kinase. The triphosphate of zidovudine appears to be the active form of the drug. Zidovudine triphosphate competes well with thymidine 5'-triphosphate for binding to the HIV reverse transcriptase and also functions as an alternative substrate. Incorporation of zidovudine monophosphate results in chain termination. However, it is not clear which mechanism, chain termination or competition with thymidine 5'-triphosphate, or a combination of both, is responsible for the inhibition of HIV replication.
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PMID:Spectrum of antiviral activity and mechanism of action of zidovudine. An overview. 304 82

Burkitt's lymphomas, linked by previous studies with the DNA-containing Epstein-Barr virus, contain an RNA related in sequence to that of Rauscher leukemia virus. The present study establishes that the viral-related RNA found in Burkitt's tumors is a 70S component encapsulated with RNA-instructed DNA polymerase in a particle possessing a density characteristic of RNA tumor viruses. Further, the DNA synthesized by the Burkitt particles hybridizes specifically to the RNA of Rauscher leukemia virus. Thus, four features characteristic of a known oncogenic RNA agent are also exhibited by particles found with a high (87%) frequency in Burkitt's tumors. The relation between the RNA particle and the Epstein-Barr virus and their etiological roles remains to be elucidated. However, relevant to these issues is the finding reported here that the presence of Epstein-Barr virus information in nonneoplastic cells does not lead to the production of the RNA particles that have been detected now in three different human neoplasias, including leukemias, breast cancer, and Burkitt's disease.
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PMID:Burkitt's tumors contain particles encapsulating RNA-instructed DNA polymerase and high molecular weight virus-related RNA. 412 90

Nucleic acid base analogues were used to examine a Herpesvirus saimiri (HVS)-infected marmoset lymphoid cell line (MLC-1) for possible association with type C viruses. Synthetic templates poly(rA).d(pT)(10) and poly(dA).d(pT)(10) were used to detect RNA-directed DNA polymerase activity in 100-fold concentrated tissue culture fluids. HVS was monitored by immunofluorescence for early, late, and membrane antigens. MLC-1 cells were exposed to 30 mug of 5-bromo-2'-deoxyuridine (BUdR) per ml for 24 h and examined daily. Similar experiments used 5-iodo-2'-deoxyuridine (IUdR) (20 mug/ml) for 30 h or IUdR (20 mug/ml) for 3 days followed by 2% dimethyl sulfoxide for 4 days. Results of these experiments failed to show any type C virus-like polymerase; however, HVS expression was greatly stimulated. BUdR and IUdR enhanced expression of HVS-associated antigens five- to sevenfold, with maximal stimulation being observed 3 to 4 days after removal of the analogue. IUdR-dimethyl sulfoxide treatment was generally less effective. Although more cells showed HVS antigens, the treatments did not increase cell-free infectious virus. The data suggest that HVS-infected lymphoid cells can be stimulated to express virus in a manner similar to that of the Epstein-Barr virus in Burkitt's lymphoma cells. No evidence of type C virus was found in stimulated cultures.
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PMID:Stimulation of Herpesvirus saimiri expression in the absence of evidence for type C virus activation in a marmoset lymphoid cell line. 413 95

Previous studies have demonstrated that Hodgkin's, Burkitt's, and other human lymphomas contain particulate elements encapsulating 70S RNA and RNA-dependent DNA polymerase. [(3)H]DNA probes endogenously synthesized by these particles were used to demonstrate that the nuclear DNA of the lymphomas contain particle-related sequences that cannot be detected (less than 1/20th of a copy per genome) in the DNA of normal cells. This result agrees with our earlier findings in human leukemias. The data are inconsistent with any etiologic concept that invokes germ-line transmission of at least one complete copy of the particulate information associated with the malignancy. The unique sequences found in the nuclear DNA of Burkitt's and Hodgkin's tissues are related to each other but not to the DNA of the Epstein-Barr virus.
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PMID:Unique nuclear DNA sequences in the involved tissues of Hodgkin's and Burkitt's lymphomas. 452 Dec 7

Peripheral blood lymphocytes from male individuals at risk for AIDS were cultured in the presence of interleukin-2. Approximately 90% of cultures originating from pre-AIDS and AIDS patients were retrovirus-positive as detected by the reverse transcriptase (RT) assay and confirmed by electron microscopy. Prolonged incubation of the retrovirus-positive cells resulted in the establishment of several interleukin-2-independent B-lymphoblastoid cell lines. These cells were positive for Epstein-Barr virus (EBV)-specific antigens and contained EBV particles. When irradiated cells from the new lines were cocultivated with an RT-negative T-cell line CEM, an efficient transmission of retrovirus was detected. The supernatants from cocultivated cells had 5-10 fold higher levels of RT activity as compared with the supernatant from the cell line alone. Type-C retroviral particles and budding structures similar to those of human T cell leukemia virus type III (HTLV-III) and lymphadenopathy-associated virus (LAV) were found by electron microscopy. HTLV-III/LAV-specific polypeptides were detected by immunoprecipitation with sera from lymphadenopathy and AIDS patients, but not with sera from healthy individuals. Our data suggest that EBV-infected B lymphocytes from individuals at risk for AIDS may serve as a biological reservoir for the AIDS-associated retrovirus.
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PMID:Establishment of retrovirus-, Epstein-Barr virus-positive B-lymphoblastoid cell lines derived from individuals at risk for acquired immune deficiency syndrome (AIDS). 608 40

The B95-8 cell line, a widely used source of highly transforming Epstein-Barr virus (EBV), obtained from the laboratory of origin, harbored an infectious retrovirus. This retrovirus generally resembled the Type D retroviruses structurally and developmentally and like the Type D retroviruses preferred Mg2+ to Mn2+ in its RNA-directed DNA polymerase reaction. Evidence for the presence of retrovirus was found in B95-8 cultures from two other sources within the United States, either by assay for polymerase or by electron microscopy. Comparison of two B95-8 cell lines showed cytogenetic differences as well as differences in retroviral activities. The results suggest that any B95-8 culture should be tested for the presence of retrovirus before its use as a source of EBV.
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PMID:Presence of retrovirus in the B95-8 Epstein-Barr virus-producing cell line from different sources. 608 97

Interactions among viruses may be significant to the pathogenesis of the profound immunologic defects observed in acquired immunodeficiency syndrome (AIDS). Such interactions could include complementary immunosuppression, potentiation of infection by altered receptors or genetic complementation, phenotypic mixing, or genetic recombination. The abnormalities induced by simultaneous infection with cytomegalovirus of Epstein-Barr virus, for example, may be synergistic and suppression induced by 1 virus may permit replication of another virus to high titer. Given the alterations in cell-surface components during the course of a viral infection, it is possible that AIDS infection modifies the expression of histocompatibility antigens on lymphocyte membranes or viral receptors not normally available on a given cell become expressed during infection with a 2nd virus. An alternative, viral potentiation, occurs when 1 virus codes for a gene product required for growth of another, resulting in a greater virus yield that would be expected from either virus alone. Phenotypic mixing occurs when 2 enveloped viruses infect the same cell, and the genome of 1 becomes incorporated in an envelope composed of glycoproteins from the other. In genetic recombination, actual exchange of genetic information between viruses allows for the emergence of new viruses with altered biologic characteristics. Such recombination occurs with high frequency in the human retroviruses, probably during a phase of replication involving reverse transcriptase to viral DNA. To learn more about such interactions, viruses isolated from the blood and semen of AIDS patients should be analyzed for cell tropism, neutralization kinetics, and hybridization.
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PMID:Possible viral interactions in the acquired immunodeficiency syndrome (AIDS). 609 5

The diterpene ester promoter of mouse skin tumors, 12-O-tetradecanoylphorbol-13-acetate (TPA), efficiently induces Epstein-Barr virus (EBV)-associated DNA polymerase (DNA nucleotidyltransferase) activity in the EBV-producing lymphoblastoid cell line, P3HR-1. With the use of intervent dilution chromatography followed by sequential DEAE-cellulose and phosphocellulose column chromatography, the virus-associated enzyme has been isolated and purified 300-fold. The partially purified EBV DNA polymerase activity could be distinguished from cellular polymerases by its activation with salt and its degree of sensitivity to N-ethylmaleimide and phosphonoacetic acid. The enzyme showed maximum activity for copying activated calf thymus DNA in the presence of 100 mM ammonium sulfate. In the absence of salt, the enzyme utilized with high efficiency deoxyoligomer-homopolymer templates, but failed to copy poly(rA) . oligo(dT)10 and oligo(dT)10, showing that the enzyme had properties distinct from DNA polymerase gamma, reverse transcriptase, and terminal deoxynucleotidyltransferase. The partially purified enzyme is strongly inhibited by acyclovir triphosphate and thus has properties similar to herpes simplex virus DNA polymerase.
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PMID:Induction of Epstein-Barr virus-associated DNA polymerase by 12-O-tetradecanoylphorbol-13-acetate. Purification and characterization. 624 99

The phenotypic characteristics of a cloned giant cell line, SU/RH-HD-1, established from the spleen of a patient with Hodgkin's disease were studied. The cells grew slowly, adhered to the culture vessel surface, and had an elongated, irregular shape. After trypsinization, they became spherical and measured 30-100 micron in diameter. Although most cells were mononuclear, binucleated and multinucleated cells could be identified in expanded cultures. The cells phagocytized latex and ink particles and were nonspecific esterase-positive, but they did not secrete lysozyme. They were Epstein-Barr nuclear antigen-negative, and their culture fluid supernatants were devoid of reverse transcriptase activity. Electron microscopy revealed cells with a pronounced smooth endoplasmic reticulum, free ribosomes, some filaments, and mitochondria. Many 0.5- to 1.0-micron invaginations (pits) were seen along the cell membrane. Nucleoli were enlarged and prominent in the very heterochromatic nuclei. The SU/RH-HD-1 cells had 10- to 100-micron-long pseudopodia that were sometimes forked or branching, as well as multiple stress fibers. Electron microscopic appearance was suggestive of that of macrophages. This interpretation of the results was substantiated by monoclonal antibody studies, which revealed that the cells express antigenic determinants distinctive for cells of the monocyte-macrophage lineage and by functional studies demonstrating that the cells are capable of specific antigen presentation to immune T-cells. The SU/RH-HD-1 cells were aneuploid and could be cloned, first in liquid culture by limiting dilution and later in semisolid medium. It was likely that the SU/RH-HD-1 cells were derived from the neoplastic giant cell population in Hodgkin's disease and that they originated from cells of the mononuclear phagocyte-reticulum cell lineage.
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PMID:Establishment and characterization of a cloned giant cell line from a patient with Hodgkin's disease. 633 36

We have examined for synergy between the IIIB strain of HIV-1 and Epstein-Barr virus (EBV) during infection of a homogeneous cell type. In order to obtain a cell population consisting of a homogeneous cell type, CD19-positive B lymphocytes were purified from human tonsils by flow cytometry. CD19-positive lymphocytes did not express detectable surface CD4 antigen. However, CD4 mRNA could be detected in CD19-positive lymphocytes by reverse transcription coupled to polymerase chain reaction and by dot blot hybridization using an antisense riboprobe. Transcription of CD4 mRNA in CD19-positive lymphocytes was suppressed by infection with the B95-8 strain of EBV and lost in B95-8-transformed lymphoblastoid cell lines. In contrast, the P3HR-1K strain of EBV had no effect on the level of CD4 mRNA. HIV-1 could infect CD19-sorted B cells as measured by accumulation of reverse transcriptase and syncytia induction after coculture with SupT1 cells. HIV-1 infection of CD19-bearing lymphocytes was blocked by OKT4a antibodies. The ability of HIV-1 to replicate in CD19-positive B lymphocytes declined following preinfection with B95-8 but not with P3HR-1K. These results as well as results with an EBNA-2 expression vector suggest that down-regulation of both CD4 mRNA and HIV-1 infection in human B cells is a function of EBV nuclear antigen EBNA-2. The fact that native CD19-positive B lymphocytes express sufficient CD4 receptor mRNA to allow HIV-1 infection strengthens the possibility that HIV-1 replication in B cells directly participates in AIDS pathogenesis. In addition, infection with EBV may modulate the ability of HIV-1 to infect and establish a latent infection in B lymphocytes in co-infected individuals.
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PMID:CD4 mRNA expression in CD19-positive B cells and its suppression by the Epstein-Barr virus. 750 84


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