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)

A mixed viral infection with a cytomegalovirus and a retrovirus in cultured guinea pig embryo (GPE) cells was investigated. The expression of an endogenous guinea pig retrovirus (GPRV) in cultured guinea pig cells was induced by a medium containing 5-bromo-2'-deoxyuridine and dexamethasone. When the induced GPE cells were superinfected with a guinea pig cytomegalovirus (GPCMV), pseudotype virions were observed. Morphological characterization of both viruses and their locations within infected cells was achieved by examination of thin sections of infected cells with transmission electron microscopy. Immunolabeling with colloidal gold particles, 5 or 15 nm in size, permitted the identification of each virus type using GPCMV- or GPRV-specific polyclonal antibodies and the detection of a population of GPCMV and GPRV particles which expressed antigens of both viruses on their envelopes. Enhanced reverse transcriptase activity of GPRV and reduced infectivity titers of GPCMV was noted in dually infected cultures. These data suggest that interaction between GPCMV and GPRV had occurred in dually infected GPE cells and that expression of GPRV was enhanced.
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PMID:Demonstration of cytomegalovirus and retrovirus pseudotypes in cultured guinea pig cells. 170 74

We examined the effects of topoisomerase inhibitors on human immunodeficiency virus type 1 (HIV-1) infection of H9 cells in cell culture. Infection is blocked or substantially reduced by the topoisomerase I inhibitor camptothecin (CPT), but not by two topoisomerase II inhibitors. Significant reduction (greater than or equal to 90%) in the amount of virus released, as measured by reverse transcriptase, is obtained if the cells are treated for 1 h with 0.01-0.02 microM CPT at the time of virus infection, and expression of viral proteins is also blocked. CPT is also shown to reduce the level of infection when chronically infected cells are cocultivated with uninfected cells. These results with CPT suggest that this compound may represent a new class of drugs with antiretroviral potential.
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PMID:Inhibition of human immunodeficiency virus (HIV-1) replication in vitro by noncytotoxic doses of camptothecin, a topoisomerase I inhibitor. 170 42

The influence of human anti-human immunodeficiency virus type 1 (HIV-1) antibody on HIV-1 infection of freshly isolated normal human peritoneal macrophages and blood monocytes was examined. Each of 14 HIV antibody-positive human serum samples was found to block the infection of four virus isolates (human T-cell lymphotropic virus type IIIBa-L [HTLV-IIIBa-L], HTLV-IIIB, D.U. 6587-7, and D.U. 7887-8) at serum dilutions ranging from 10(-1) to 10(-2). Three of these isolates (HTLV-IIIBa-L, D.U. 6587-7, and D.U. 7887-8) infected cultures of monocytes and macrophages rapidly and produced high levels of virus reverse transcriptase and p24 antigen. A fourth virus isolate (HTLV-IIIB) infected the monocytes and macrophages more slowly and produced low levels of viral protein. More dilute HIV antibody-positive sera had no significant effect on the overall level or rate of virus infection or expression. Complement did not appear to influence the course of infection by any combination of antisera or virus examined. Successful HIV-1 infection of the peritoneal macrophages and blood monocytes under the conditions tested showed strict dependence on CD4 since a recombinant CD4 polypeptide and an anti-CD4 monoclonal antibody effectively blocked the process.
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PMID:Lack of enhancing effect of human anti-human immunodeficiency virus type 1 (HIV-1) antibody on HIV-1 infection of human blood monocytes and peritoneal macrophages. 171 61

Human blood-borne monocytes (MO) differentiating into mature macrophages (MAC) were cultured on hydrophobic Teflon membranes. The cells were infected with two different monocytotropic HIV isolates: HIV1D117III obtained from a perinatally infected child, and HIV2D194 obtained from an AIDS patient who suffered exclusively from neurological symptoms. Virus production monitored by reverse transcriptase activity and HIV-antigen ELISA in cell-free supernatant was of a high level and continued for several weeks. To investigate possible modulatory pathways interfering with HIV infection in MAC we tested various recombinant cytokines as well as bacterial lipopolysaccharides (LPS) in our culture system. Whereas interleukin-1 (IL1) accelerated and increased HIV replication in MO/MAC, the interferons (IFN) alpha, beta and gamma effectively suppressed or delayed infection depending on the concentration used. Suppression was seen at concentrations as low as 0.3 U/ml and was most effective when the IFN were given prior to infection. No effect was observed with IL6 up to 2,000 U/ml. LPS affected virus infection in a complex manner: at 1-100 ng/ml virus replication was inhibited, but it was enhanced at subnanogram concentrations (25-100 pg/ml).
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PMID:Effect of cytokines and lipopolysaccharides on HIV infection of human macrophages. 171 76

The antibody response in cats to feline immunodeficiency virus (FIV) reverse transcriptase (RT) was followed for 3 years. Eight of the nine cats used in this study produced reverse transcriptase-inhibiting (RTI) antibodies. Relative inhibitory means of 2.9%, 18.4%, 33%, and 47% were found 6, 12, 24, and 36 months, respectively, after infection with FIV. The enzyme activity was suppressed by greater than or equal to 78% with the use of 100 micrograms of FIV-associated IgG. The RTI antibodies were FIV-specific, as they did not inhibit other mammalian retroviral polymerases, including feline leukemia virus RT. An RT-inhibition assay with sera in the presence of protein A and immunoblot analysis showed that antibody binding to FIV RT protein p62 is independent of antibody ability to block enzyme activity. Viral RT released by detergent-treated virus was stable for more than 6 weeks at 4 degrees C, whereas its activity was reduced by 50% after 2 weeks at 37 degrees C. Because significant concentrations of RTI antibodies are detected only at 1 to 2 years after infection, they can be used to determine the approximate time of virus infection and as a marker for disease progression.
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PMID:Antibody response to reverse transcriptase in cats infected with feline immunodeficiency virus. 172 99

The Rauscher murine leukemia retrovirus system provides an in vivo model of the human acquired immune deficiency syndrome for testing the ability of antiviral agents and biological response modifiers (BRM) to suppress viremia and retroviral disease. In the present report we examined three agents in the Rauscher retrovirus model: imexon, Ampligen and poly[I,C]-LC. Imexon reduced splenomegaly, viremia, and serum reverse transcriptase levels even when treatment was not initiated until 7 days after virus infection. Imexon also significantly prolonged the survival of infected mice. Thus it proved to be an effective antiviral agent in this system, although imexon did not completely eliminate retroviral infection in treated mice. Poly[I,C]-LC and Ampligen had immunomodulatory effects. Both of these BRM augmented the cytolytic activity of splenic natural killer (NK) cells in infected animals when treatment was initiated 24 h after infection. Poly[I,C]-LC had antiretroviral activity when administered on this schedule. In order to examine the role of NK cell augmentation in the antiviral activity of poly[I,C]-LC, we attempted to deplete NK activity by treatment with rabbit antibody to asialo GM1, a ganglioside on the surface of murine NK cells. Combined treatment of infected mice with poly[I,C]-LC and anti-asialo GM1 decreased the antiviral activity of poly[I,C]-LC. This finding suggests that NK cells may be involved in the antiviral effect of this BRM.
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PMID:Imexon and biological response modifiers in murine models of AIDS. 182 6

In contrast to T-cell lines, where CD-4 expression may predict susceptibility to HIV infection, in monocyte hybridomas, presence or absence of surface CD-4 does not appear to be the determining factor of susceptibility to HIV infection. One clone, 20, was documented to be CD-4 negative by surface immunofluorescence as well as by immunoprecipitation. Both CD-4+ and CD-4- human monocyte hybridomas, representative of peripheral blood monocytes were readily infected with HIV (strains IIIB and BR-1 and a variety of patient isolates) as assessed by p24 Ag secretion reverse transcriptase activity and in situ hybridization. Infection occurred in the absence of antibody to HIV suggesting a non Fc mediated process as had been previously described. These data suggest that alternative mechanisms, such as non-specific phagocytosis, may exist for entry of HIV into peripheral blood monocytes. Given these findings, treatment for AIDS, such as the use of soluble CD-4, may not be effective long term, as monocyte infection may still occur and serve as a reservoir for subsequent viral infection of T cells.
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PMID:Surface expression of CD-4 does not predict susceptibility to infection with HIV-1 in human monocyte hybridomas. 196 58

Phase I and II clinical studies have been conducted to test the safety and potential activity of the reverse transcriptase inhibitor, dideoxycytidine (ddC), in treating human immunodeficiency virus-1-infected patients. Although ddC appears to be active in combating viral infection, as judged by its ability to decrease human immunodeficiency virus-1 p24 antigen titers and increase the number of CD4+ lymphocytes, it is also capable of causing severe peripheral neuropathy in a dose-dependent manner. The studies discussed here indicate that low-dose ddC treatment regimens substantially reduce the toxic side effects of this drug, and yet retain the ability to affect p24 antigen and CD4+ lymphocyte levels. These studies also define the window of therapeutic usefulness for ddC, and suggest that both safety and activity can be maintained during long-term, low-dose use of ddC.
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PMID:Safety and tolerance of dideoxycytidine as a single agent. Results of early-phase studies in patients with acquired immunodeficiency syndrome (AIDS) or advanced AIDS-related complex. Study Group of the AIDS Clinical Trials Group of the National Institute of Allergy and Infectious Diseases. 215 3

Mononuclear phagocytes can be infected with the human immunodeficiency virus type 1 (HIV-1). Although these cells express CD4 antigen, which is the recognized cellular receptor for HIV, additional cell surface proteins such as the Fc receptor, might serve as receptors for infection. In order to study this possibility we used the U937 monocytic cell line as a target for HIV infection. Flow cytometry of U937 showed that 97% of cells expressed CD4, 33% expressed the high affinity 72 kD Fc receptor (FcRI), and 74% expressed the low-affinity 40 kD Fc receptor (FcRII). Virus neutralization tests were performed by preincubating heat-inactivated human anti-HIV sera with HIV-1, IIIB strain, and then challenging U937. After 13 days in culture, productive HIV-1 infection was monitored by reverse transcriptase activity. High concentrations of certain sera (10(-1)-10(-3) dilutions) neutralized HIV-1, but at subneutralizing concentrations (10(-4)-10(-6) dilutions), five of these sera enhanced viral infection approximately two- to threefold. This enhancement of HIV-1 infection was totally blocked by 1 microgram/ml recombinant soluble CD4 (rCD4) or by 0.5 microgram/ml anti-CD4 Leu3a monoclonal antibody. These results suggest that serum enhancement of HIV-1 infection, thought to be due to binding to the monocyte Fc receptor, requires HIV-1 binding to CD4, since rCD4 or Leu3a blocked this phenomenon.
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PMID:Inhibition of serum-enhanced HIV-1 infection of U937 monocytoid cells by recombinant soluble CD4 and anti-CD4 monoclonal antibody. 236 Oct 75

The recent discovery of HTLV-III, a cytopathic member of the family of human T-cell lymphotropic viruses (HTLV), and its identification as the etiological agent of acquired immunodeficiency syndrome (AIDS) have important implications for the treatment of this disorder. The pathogenesis of AIDS involves the destruction of helper/inducer T-lymphocytes by active viral infection, and drugs which inhibit the replication of HTLV-III or monoclonal antibodies directed at viral antigens may be important components of future therapeutic strategies. There are a number of steps in the replication of HTLV-III which might potentially be susceptible to antiviral agents. One drug, suramin, which was originally developed as an antitrypanosomal agent, has been found to be an inhibitor of reverse transcriptase. This drug has been shown to block the infectivity and cytopathic effect of HTLV-III [Mitsuya, H., Popovic, M., Yarchoan, R., Matsushita, S., Gallo, R. C., and Broder, S. Science (Wash. DC), 266: 172-174, 1984]; in addition, it is able to block the in vitro replication of another member of the HTLV family, HTLV-I, at concentrations of 25 to 75 micrograms/ml. Lymphocyte proliferation in vitro is minimally inhibited at these concentrations of suramin, and the ratios of helper/inducer to cytotoxic/suppressor T-lymphocytes are not affected. Clinical trials are being initiated to study the effect of suramin on patients with AIDS. Evaluation of this and other antiviral treatments for AIDS will optimally involve direct assessment of its effects on HTLV-III replication in vivo. Recent evidence, however, suggests that these patients have a low level of viral replication in lymphoid tissue which may spontaneously fluctuate, making such evaluation complex.
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PMID:Implications of the discovery of HTLV-III for the treatment of AIDS. 241 Jan 13


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