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)

Feline immunodeficiency virus (FIV) has morphological, physical and biochemical characteristics similar to human immunodeficiency virus (HIV), the cause of AIDS in man. However, it is antigenically and genetically distinct from HIV; an antigenic relatedness with equine infectious anaemia virus has been demonstrated. FIV has been molecularly cloned and sequenced. Diagnostic tests are commercially available and attempts at preparing inactivated, subunit and molecularly engineered vaccines are being made in different laboratories. During FIV infection a transient primary illness can be recognized, with fever, neutropenia and lymphadenopathy. After a long period of clinical normalcy a secondary stage is distinguished with signs of an immunodeficiency-like syndrome. The incubation period for this stage can be as long as 5 years, during which gradual impairment of immune function develops. Many FIV-infected cats are presented for the first time showing vague signs of illness: recurrent fevers, emaciation, lack of appetite, lymphadenopathy, anaemia, leucopenia and behavioural changes. Later, the predominant clinical signs observed are chronic stomatitis/gingivitis, enteritis, upper respiratory tract infections, and infections of the skin. Neoplasias, neurological, immunological and haematological disorder are seen in a smaller proportion. The immunodeficiency-like syndrome is progressive over a period of months to years. Concomitant infection with feline leukaemia virus has been shown to accelerate the progression of disease. In vitro, phenotypic mixing between FIV and an endogenous feline oncovirus (RD114) has been demonstrated which leads to a broadening of the cell spectrum of the lentivirus. Bovine immunodeficiency virus (BIV) has been isolated only once, and all attempts to obtain additional isolates have failed; it has been recovered from the leucocytes of cattle with persistent lymphocytosis, lymphadenopathy, lesions in the central nervous system, progressive weakness and emaciation. As with the feline representative, BIV also was found to possess a lentivirus morphology and to encode a reverse transcriptase with Mg++ preference; it replicates and induces syncytia in a variety of embryonic bovine tissues in vitro. Antigenic analyses have demonstrated a conservation of epitopes between the major core protein of BIV and HIV. The original isolate has been molecularly cloned and sequenced. Besides the three large open reading frames (ORFs) comprising the gag, pol, and env genes common to all replication-competent retroviruses, five additional small ORFs were found. Numerous point mutations and deletions were found, mostly in the env-encoding ORF. These data suggest that, within a single virus isolate, BIV displays extensive genomic variation.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Animal immunodeficiency viruses. 133 43

Fifty-seven HIV-1 strains were isolated from peripheral blood lymphocytes of 102 HIV-infected persons involved in epidemic outbreaks in different cities of the USSR. The effectiveness of isolation was 29.1% in asymptomatic infection, 51.7% in cases with generalized lymphadenopathy, and 82.6% in persons with severe clinical manifestations. Identification of the isolates by indirect immunofluorescence, ELISA, reverse transcriptase activity, Western blot, electron microscopy, and polymerase chain reaction showed them to belong to HIV-1 type. Reproduction of the isolates in cell cultures was accompanied by cytopathic effect and syncytium formation. The isolated strains can be divided into two groups: (1) the poorly growing isolates with low or negative RT and ELISA results and (2) the isolates with high infectivity, broad spectrum of cell tropism, and high levels of RT and ELISA. These data show the correlation of biological properties of HIV-1 strains isolated in the USSR with those of HIV strains previously isolated in Europe, USA, and Africa.
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PMID:[The characteristics of human immunodeficiency virus strains isolated from HIV-infected persons on the territory of the USSR]. 138 38

A double-blind, randomized, placebo-controlled trial comparing two daily doses of oral ribavirin (600 and 800 mg) and a placebo was performed at four medical centers geographically distributed throughout the USA. One hundred and sixty-four HIV-infected adult men with lymphadenopathy were enrolled over a 2-month period and received active treatment for 24 weeks followed by a 4-week interval during which they did not receive the study drug. A marked interlaboratory variation in HIV isolation from peripheral blood mononuclear cells was observed, underscoring the critical role of quality assurance in similar multicenter trials. Nevertheless, the combined data indicate that ribavirin did not significantly suppress HIV activity (on measurement of reverse transcriptase activity) after week 6 or reduce serum p24 antigenemia.
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PMID:A multicenter clinical trial of oral ribavirin in HIV-infected people with lymphadenopathy: virologic observations. Ribavirin-LAS Collaborative Group. 169 May 51

An antimicrobial peptide, tachyplesin I, isolated from hemocytes of the Japanese horseshoe crab (Tachypleus tridentatus) was examined for its inhibitory effects on human immunodeficiency virus (HIV) infection in vitro. At a concentration of 7.5 micrograms/ml, tachyplesin I suppressed the development of cytopathic effects (CPE) by more than 70% in MT-4 cells infected with HIV (lymphadenopathy-associated virus). This inhibitory effect was observed only when the drug was added during the adsorption period of the virus to the cells. In cocultures of MOLT-4 and persistently HIV-infected cells (MOLT-4/HIV), tachyplesin I at the same concentration completely inhibited multinucleated giant cell formation. Infectivity of HIV was reduced by 10(-2.5) in medium free from fetal calf serum containing tachyplesin I at a concentration of 200 micrograms/ml. Tachyplesin I did not show any inhibitory effect on reverse transcriptase activity of HIV at concentrations of 9-80 micrograms/ml at which tachyplesin I inhibited HIV infection. These results suggest that the anti-HIV action of tachyplesin I was due to the inhibition of virus adsorption.
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PMID:Inhibitory effect of tachyplesin I on the proliferation of human immunodeficiency virus in vitro. 188 8

Multinucleated giant cells (MGCs) were detected in cell lines established from peripheral blood lymphocytes of patients with: (a) acquired immunodeficiency syndrome (AIDS) and lymphadenopathy syndrome (LAS), (b) chronic active hepatitis (CAH), (c) papular acrodermatitis (PA) negative for hepatitis B virus antigens but positive for EBV, and (d) epidermolysis bullosa acquisita positive for EBV. All the cell lines established, including those established from AIDS and LAS patients, were examined for the presence of human immunodeficiency virus (HIV) by indirect immunofluorescence with monoclonal antibodies directed against the HIV antigens p17 and p24 and for the presence of reverse transcriptase. All the cell lines were found to be negative for HIV. While the cell lines obtained from AIDS patients still express MGCs after more than two years in culture, their supernatants are negative for reverse transcriptase activity and carry phenotypic markers characteristic of B cells. From the LAS and chronic active hepatitis patients we obtained a monolayer of adherent cells almost completely represented by MGCs that lasted for six and four months, respectively. After this period of time a proliferation process took place. Both the cell lines obtained carry B cell phenotypic markers, but MGCs are still a characteristic only for the LAS-derived cell culture. Non infected patients or normal subjects express MGCs only during the early stage of the cultue. The correlation between the presence of MGCs and a retrovirus infection is discussed in the light of the role of MGCs in the pathogenesis of AIDS.
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PMID:High expression of multinucleated giant cells in cultures of peripheral blood cells from HIV infected patients. 222 16

The acquired immune deficiency syndrome (AIDS) is thought to result from infection of T cells by a pathogenic human retrovirus, human T-lymphotropic virus type III (HTLV-III) or lymphadenopathy-associated virus (LAV). In this report, we describe the antiviral effects of a thymidine analogue,3'-azido-3'-deoxythymidine (BW A509U), which, as a triphosphate, inhibits the reverse transcriptase of HTLV-III/LAV. This agent blocks the expression of the p24 gag protein of HTLV-III/LAV in H9 cells following exposure to virus. The drug also inhibits the cytopathic effect of HTLV-IIIB (a virus derived from a pool of American patients) and HTLV-III/RF-II (an isolate obtained from a Haitian patient that differs by about 20% in the amino acid sequence of the envelope gene from several isolates of HTLV-III/LAV, including HTLV-IIIB, analyzed so far). 3'-Azido-3'-deoxythymidine also completely blocks viral replication as assessed by reverse transcriptase production in normal human peripheral blood mononuclear cells exposed to HTLV-IIIB. Finally, at concentrations of 3'-azido-3'-deoxythymidine that block the in vitro infectivity and cytopathic effect of HTLV-IIIB, the in vitro immune functions of normal T cells remain basically intact.
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PMID:3'-Azido-3'-deoxythymidine (BW A509U): an antiviral agent that inhibits the infectivity and cytopathic effect of human T-lymphotropic virus type III/lymphadenopathy-associated virus in vitro. 241 59

Suramin and various other selected compounds were evaluated for their in vitro inhibitory effects on the infectivity and replication of human T-cell lymphotropic virus (HTLV/III)/lymphadenopathy-associated virus (LAV). As parameters for infectivity and replication, respectively, we followed the cytopathic effect of HTLV-III/LAV on ATH 8 cells, a T-cell clone with high susceptibility to HTLV-III/LAV, and the expression of HTLV-III/LAV p24 gag protein in H9 cells infected with HTLV-III/LAV. As the most effective inhibitors of HTLV-III/LAV the following substances emerged (in order of decreasing activity): Evans Blue approximately equal to suramin greater than phosphonoformic acid greater than Direct Yellow 50. Several purine nucleoside analogues including vidarabine, tubercidin, neplanocin A, dihydroxypropyladenine, pyrazofurin and ribavirin were not inhibitory to HTLV-III/LAV. In our test systems, involving a high multiplicity of infection, HPA-23, previously reported to be effective against LAV reverse transcriptase, showed no inhibitory effect on HTLV-III/LAV infectivity for ATH 8 cells and proved only weakly inhibitory to HTLV-III/LAV replication in H9 cells. Thus, among the anionic dyes that are structurally related to suramin, compounds were found which were as active as suramin itself, if not more so.
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PMID:Comparative inhibitory effects of suramin and other selected compounds on the infectivity and replication of human T-cell lymphotropic virus (HTLV-III)/lymphadenopathy-associated virus (LAV). 241 66

We developed cloned populations from the commonly available, well-characterized cell line HUT-78. These cloned cells grow permanently after infection with isolates of human T-lymphotropic virus type III, also called lymphadenopathy virus (HTLV-III/LAV), from patients with acquired immune deficiency syndrome and related syndromes. In contrast, activated human T cells are lysed after HTLV-III/LAV infection. The infected cloned cells have been in culture continuously for 6 months and have produced high levels of extracellular reverse transcriptase (400,000 cpm/ml). This level is comparable to that of similarly infected normal human T cells. Three weeks after infection with HTLV-III/LAV, more than 90% of the cloned HUT-78 cells lysed; the remaining cells continued to grow. Approximately 80% of these cells expressed HTLV-III/LAV antigens by immunofluorescence. The extracellular virus of the chronically infected cell line was shown to be similar to other HTLV-III/LAV isolates by competition radioimmunoassay, by reactivity with human serum, and by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. This HTLV-III/LAV-infected immortalized cell line enables the continuous production of large amounts of virus.
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PMID:Continuous production of a cytopathic human T-lymphotropic virus in a permissive neoplastic T-cell line. 242 5

The human T-lymphotropic virus type III/lymphadenopathy-associated virus (HTLV-III/LAV) requires reverse transcriptase for viral replication. We treated 12 patients who had acquired immunodeficiency syndrome and active HTLV-III/LAV viremia with suramin, a potent competitive inhibitor of reverse transcriptase, in six weekly induction doses of 1 g, followed by weekly maintenance doses of 500 mg. Three of eleven evaluable patients had complete inhibition of viral reverse transcriptase levels, lasting at least 18 weeks in each. Two additional patients had marked reduction in reverse transcriptase activity. Nadir serum suramin levels at the end of the induction phase correlated with the level of reverse transcriptase reduction. Toxicity included hepatic transaminase elevation, fever, malaise, rash, proteinuria, paresthesias, reversible neutropenia, and adrenal insufficiency. Objective clinical improvement was documented in 1 patient, but no patient had improvement in immune function and 7 patients had recurrent opportunistic infections. Although suramin may suppress HTLV-III/LAV viremia, its significant toxicity and lack of effect on immune variables indicate that alternative therapy will be required.
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PMID:Suramin antiviral therapy in the acquired immunodeficiency syndrome. Clinical, immunological, and virologic results. 242 53

Kawasaki disease (KD) is an acute vasculitis of infancy and early childhood characterized by high fever, rash, mucositis, lymphadenopathy and coronary artery damage. Large epidemics have been described in Japan and the United States and the number of cases reported annually is steadily increasing. The aetiology of KD is unknown. During the acute phase of the disease marked immunologic alterations occur including generalized T-cell lymphocytopenia, activation of circulating T4+ helper T cells, decreased numbers of T8+ suppressor T cells and marked B-cell activation. We postulated that a lymphotropic virus with affinity for endothelial and lymphoid cells might explain the vasculitis and immunological abnormalities in KD. We report here our study of the particulate fraction from culture supernatants of peripheral blood mononuclear cells (PBMC) for evidence of retrovirus-associated reverse transcriptase (RT) activity. Activity was found in the supernatants from KD patients but not control cultures. This RT activity was transmitted to an established T-cell line (HUT-78) and thus may be due to an exogenous agent infecting KD lymphocytes.
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PMID:Polymerase activity in lymphocyte culture supernatants from patients with Kawasaki disease. 243 Jan 87


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