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)

Infection with the human immunodeficiency virus (HIV) is often followed by a prolonged latent state, and mechanisms of maintaining latency or inducing expression from latency are active areas in AIDS research. It has been previously shown using a variety of viruses and cell systems that ultraviolet (UV) irradiation is capable of inducing the expression of latent viruses as well as augmenting the effects of acute viral infection. The ability of UV irradiation to affect HIV latency was investigated using a chronically HIV-infected, virus nonexpressing promonocytic cell line termed U1. After exposure to UV-C in doses ranging from 0.75 to 2.0 mJ/cm2, U1 cells were induced to express virus as assessed by detection of elevated reverse transcriptase activity and p24 antigen levels in culture supernatants of treated cells compared with unstimulated controls. In addition, immunofluorescence on cytospin preparations of UV-irradiated cells revealed a time-dependent increase in viral antigen production after UV stimulation. A similar increase in RT levels was seen after exposure of U1 cells to UV-B, although somewhat higher doses of UV-B (mJ) were required compared with UV-C (mJ). Viral induction by UV irradiation was associated with a drop in viability and a static growth curve, suggesting that a certain level of cellular stress was most likely necessary to initiate viral expression. The potential role of UV-induced cell damage with activation of a cellular "SOS" repair response is a probable explanation of the enhanced viral production observed.
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PMID:Induction of expression of human immunodeficiency virus in a chronically infected promonocytic cell line by ultraviolet irradiation. 247 51

The expression of CD4 antigen on the surface of LeuM3-positive human blood monocytes was found to be variable with 65 to 90% of cells from 46 normal human volunteers being positive by dual staining flow cytometry. When monocytes adhered to plastic (but not when cultured on Teflon), a marked decrease in CD4 expression was observed between 1 and 24 h post-adherence. CD4 expression could not be detected in macrophages adhered to plastic for 5 days by using four anti-CD4 monoclonal antibodies in flow cytometry or direct immunofluorescence. Conversely an increasing proportion of adherent cells expressed LeuM3 and OKM5 surface antigens over the 5 days. CD4 mRNA levels were measured by slot-blot and Northern hybridization, and total cellular CD4 protein levels by immunoprecipitation. Both cellular mRNA and CD4 levels remained constant throughout the 5 day period but membrane CD4 protein levels were greatly reduced indicating that the down-regulation of CD4 was post-translational. Infection with two of six fresh human immunodeficiency virus (HIV) isolates showed different kinetic patterns when tested on purified monocytes recently adhered to plastic and macrophages adherent for 5 days. HIV antigen and reverse transcriptase levels in infected monocyte cultures remained high for 3 to 4 weeks before detachment and necrosis of the cells occurred. Infection of macrophages generated much lower levels of antigen and reverse transcriptase which declined to very low or undetectable levels over 2 weeks, leaving persisting viable macrophages. One week after infection HIV nucleic acid was detected in 69 +/- 7% of monocytes and 6 +/- 3% of macrophages by in situ hybridization. Blocking experiments with anti-Leu3a monoclonal antibody suggested that HIV infection of 5 day adherent macrophages occurred mainly by a mechanism other than binding to CD4.
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PMID:Variations in CD4 expression by human monocytes and macrophages and their relationships to infection with the human immunodeficiency virus. 267 36

A detailed definition of AIDS virus-specific T lymphocytes will require the generation and characterization of HIV-1-specific, cloned T cell populations. In our studies, we show that CD8+CD4- lymphocyte lines, derived from PBL of rhesus monkeys infected with simian immunodeficiency virus of macaques and humans infected with HIV-1, can harbor AIDS viruses. CD8+CD4- lymphocyte lines derived from infected individuals are shown to express AIDS virus-encoded proteins and generate reverse transcriptase activity. Infection of these CD8+CD4- lymphocytes is confirmed at the single cell level by the techniques of immunoelectronmicroscopy and two-color immunohistochemistry. This observation suggests that it may prove problematic to generate cloned, functional T lymphocyte populations from AIDS virus-infected individuals and raises the possibility that CD8+CD4- cells may serve as reservoirs for the AIDS viruses.
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PMID:CD8+CD4- lymphocyte lines can harbor the AIDS virus in vitro. 280 10

Infection of normal peripheral blood T cells by the acquired immune deficiency syndrome (AIDS)-associated retrovirus (ARV) was evaluated in long-term cultures of helper-inducer T cells (T4 cells). Cells that were inoculated with ARV and maintained in medium supplemented with interleukin-2 remained productively infected with this virus for more than 4 months in culture, although they showed no cytopathic effects characteristic of acute ARV infection. The presence of replicating virus was demonstrated by reverse transcriptase activity of culture fluids and by viral antigens and budding particles detected on cells by immunofluorescence and electron microscopy. Virus produced in these cultures remained infectious and could induce cytopathic effects and viral antigens in uninfected lymphoid cells. The finding that normal lymphocytes may be productively infected by an AIDS retrovirus in the absence of cell death suggests that a range of biologic effects may occur after infection in vivo.
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PMID:Persistent noncytopathic infection of normal human T lymphocytes with AIDS-associated retrovirus. 299 22

It has been recently established that AIDS is a virus infectious disease. HTLV-I essentially makes T4 lymphocytes malignant and induces their abnormal proliferation. However, on the way, when HTLV-I induces a decrease in the function of T4 lymphocytes, the symptoms of ARC or AIDS take place on occasion. HTLV-III/LAV possesses a central function to destroy T4 lymphocytes, but, when this function is blocked, it increases T4 lymphocyte proliferation. Accordingly, the concept of carriers of the AIDS virus and patients with AIDS-related complex or AIDS has been clarified. Simultaneously, it has been discovered that a multiplicity of amino acids exists on the envelope of isolated AIDS viruses, resulting in a variety of viral envelope antigenicities. This may support the presence of antigenic modulation, which might make the development of a vaccine more difficult. Therapy has been approached from the following points of view; blockers of reverse transcriptase, drugs for destroying the virus itself through the viral envelope, vaccination, replacement of patient's T4 lymphocytes with healthy bone marrow, and use of immunopotentiators.
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PMID:[AIDS--a further development]. 301 Aug 82

Viral infections, predominantly those of the herpes virus family, account for up to 16% of all clinically significant infections in AIDS patients. Acyclovir has provided successful treatment in AIDS patients suffering from severe herpes simplex and herpes zoster virus infections. Preliminary results are presented on newly developed acyclovir analogues. Desciclovir, an oral prodrug of acyclovir which is metabolized to acyclovir in vivo, allows treatment of virus infections per os, where high serum levels are needed, e.g. in Epstein-Barr virus infections. BW B759U, another analogue of acyclovir, has been used for the treatment of life-threatening or sight-threatening cytomegalovirus infections in AIDS patients. More than 80% of the patients treated for retinitis experienced stabilization or clinical improvement. Antiviral efficacy was demonstrated in 73% of the patients. Azidothymidine, a nucleoside analogue of thymidine, has been developed specifically to treat the HIV infection. Its antiviral activity is based on inhibition of reverse transcriptase. Phase I studies have demonstrated that azidothymidine is well tolerated. Its ability to cross the blood brain barrier makes it an attractive candidate for treatment of HIV. Trials to determine efficacy are in progress.
Infection 1987
PMID:Management of viral infections in AIDS patients. 303 16

After infection of the respective target cells with the human immunodeficiency virus (HIV-1) viral progeny is produced only after a short temporary delay of some days, depending on cell type. After this period of time a sudden onset of HIV-1 protein synthesis with a dramatic increase in virus release occurs. (2'-5')Oligoriboadenylates [(2'-5')A], capable to activate a latent ribonuclease (RNase L) degrading both mRNA and rRNA, are known mediators involved in the early response of cells to virus infection. Here we show that the (2'-5')A-synthesizing (2'-5')A synthetase, which is inducible by interferon and activated by double-stranded RNA, as well as a (2'-5')A nuclease (2',3'-exoribonuclease) are associated with the nuclear matrix of uninfected and infected H9 cells, also in the absence of interferon. Infection of H9 cells with HIV-1 was found to cause a strong (7.7-fold) enhancement of (2'-5')A synthetase activity and a smaller (2-fold) increase of 2',3'-exoribonuclease activity. Simultaneously the concentration of synthesized (2'-5')A increased 5 to 10 times in isolated nuclei. After incubation for 2 to 3 days both enzyme activities reached a maximum and then dropped below their initial values. Concomitantly a drastic increase in virus production occurred, as judged by reverse transcriptase activity in the culture fluid. These results suggest that the (nuclear matrix-associated) (2'-5')A system might be important during the initial stage of HIV infection, also by destructing matrix-bound viral messengers.
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PMID:Alteration of nuclear (2'-5')oligoriboadenylate synthetase and nuclease activities preceding replication of human immunodeficiency virus in H9 cells. 322 94

Primary cultures from a brain biopsy specimen of a human T-cell lymphotropic virus type III/lymphadenopathy-associated virus (HTLV-III/LAV) seropositive patient with progressive dementia contained small numbers of monocytoid cells and showed reverse transcriptase activity that persisted for as long as 100 days. Electron microscopy of these cells revealed the presence of HTLV-III/LAV virions. Subcultured cells removed from primary cultures by trypsinization were nonspecific esterase negative and did not express virus or show evidence of HTLV-III/LAV proviral sequences, while those remaining in the original flasks were nonspecific esterase positive and continued to produce virus. Virus from primary cultures was transmitted to peripheral blood-derived monocyte-macrophages and T cells. Virus production in T-cell cultures was transient while the monocyte-macrophages, like the primary cultures, produced virus for at least 120 days. Infection of several brain-derived cells with this and another HTLV-III/LAV isolate failed to demonstrate virus replication. These results indicate that the HTLV-III/LAV-infected cells recovered from the brain of this patient are cells of the mononuclear phagocyte series.
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PMID:Virus isolation from and identification of HTLV-III/LAV-producing cells in brain tissue from a patient with AIDS. 349 May 87

Infection of human helper T lymphocytes with the human immunodeficiency virus (HIV) results in a rapid induction of cytopathic effects and cell lysis. We isolated a variant of the human T-lymphoblastoid cell line, CEM, that is fully susceptible to HIV infection but resistant to virally induced cytopathic effects. Exposure of the cells, designated CR-10, to HIV resulted in the expression of viral antigens in 100% of cells within 6-9 days. Virus-infected cells remained fully viable and could be cultivated under standard culture conditions for a desired period of time. Parental CEM cells died within 9-12 days after HIV infection. Proviral DNA could be detected in the HIV-infected CR-10 cells by Southern blot and molecular hybridization 4-5 days after infection; the relative amount of proviral DNA reached maximum at Days 6-10 and remained stable during an 8-month follow-up period. Virus production by HIV-infected CR-10 cells was documented by electron microscopy and detection of reverse transcriptase activity in cell culture supernatants. HIV-infected CR-10 cells exhibited a down modulation of the OKT-3, OKT-4, OKT-4A, OKT-8, and OKT-11 T-cell surface markers, but not of the OKT-9 (transferrin receptor). One of the HIV persistently infected CR-10 cell clones has been kept in continuous culture for over 8 months. During this period, the cells remained fully viable, 100% positive for HIV antigens, and negative for most of the T-cell surface markers tested and continued to produce biologically active HIV. The CR-10 and HIV-infected CR-10 cell lines will be useful in studies on the biology of HIV and in the isolation and large-scale propagation of this virus.
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PMID:A human T-cell line resistant to cytopathic effects of the human immunodeficiency virus (HIV). 349 10

Chicken embryo cells normally contain, in addition to deoxyribonucleic acid (DNA)-dependent DNA (D-DNA) polymerases, a novel "R-DNA-polymerase" which specifically copies polyriboadenylic acid strands. This R-DNA polymerase cannot copy natural ribonucleic acid or polyribocytidylic acid strands to a significant extent. Infection of cells with the leukovirus RAV-2 leads to the intracellular formation of large amounts of the viral RNA-dependent DNA polymerase whose properties differ from the cell R-DNA polymerase. Chicken cells transformed by a Rous sarcoma virus mutant which produce noninfectious alpha-type Rous sarcoma virus (f), a leukovirus known to be deficient in the viral RNA-dependent DNA polymerase, do not contain detectable viral RNA-dependent DNA polymerase, whereas the cellular R-DNA polymerase is found in normal amounts. There seems to be no relationship between the cellular R-DNA polymerase and the RNA-dependent DNA polymerase of the avian leukoviruses.
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PMID:Deoxyribonucleic acid polymerase activities in normal and leukovirus-infected chicken embryo cells. 411 36


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