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)

An infectious virus which causes persistent lymphocytosis, lymphadenopathy, lesions in the central nervous system (CNS), progressive weakness and emaciation was previously isolated from the leukocytes of cattle. Our present studies show that this virus encodes a reverse transcriptase (RT) with Mg2+ cation preference, replicates and induces syncytia in a variety of embryonic bovine tissues in vitro, and has a morphology most similar to the human immunodeficiency virus (HIV). Moreover, serologic analyses have demonstrated a conservation of epitopes between the major core protein of this bovine retrovirus and HIV. Shared antigenic determinants were also observed with other pathogenic retroviruses of the lentivirus subfamily. To resolve the phylogenetic relationship of this virus, proviral molecular clones were derived and used to determine the nucleotide sequence of the highly conserved RT domain. The sequence data and serologic analyses together show that this bovine retrovirus is a novel lentivirus related to HIV and other lentiviruses. We propose that this virus be tentatively named bovine immunodeficiency-like virus (BIV) to reflect its genetic relationship and biological similarity to HIV.
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PMID:Characterization and molecular cloning of a bovine lentivirus related to human immunodeficiency virus. 368 55

LAV/HTLV-III has been closely linked to the acquired immunodeficiency syndrome (AIDS). We have studied and correlated the prevalence of AIDS-associated retrovirus and retroviral antibodies in several groups of male homosexuals from Greenwich Village. Retrovirus was detected in cultured peripheral blood lymphocytes by testing for reverse transcriptase (RT) and confirmed by establishment of virus-producer cell lines, and electron microscopy. Seventy-six percent of patients with AIDS, 93% with AIDS-related complex (ARC), 69% with generalized lymphadenopathy (LAS), and 35% of asymptomatic homosexuals were positive for virus in the RT assay. Transmission of the virus from RT-positive lymphocytes into the CEM cell line was successful in 10 of 11 randomly chosen cases. No virus isolates were obtained from lymphocytes of 8 heterosexual individuals. Serum antibodies against AIDS-associated virus were detected by indirect immunofluorescence assay and confirmed by Western blotting, using an LAV/HTLV-III-producer cell line, LAV-N1, which we established. LAV/N1 virus was purified by ultracentrifugation through sucrose gradient and the pattern of its proteins was determined by SDS-gel electrophoresis and Western blotting using sera from an AIDS patient. The major polypeptides of LAV/HTLV-III (19, 25-27, 32, 42 and 54 kilodalton) were present. These proteins did not react in Western blots with sera positive for Adult T cell leukemia virus (ATLV). thus, LAV-N1 and ATLV were not antigenically related. In our assay for LAV/HTLV-III antibodies, 18 (100%) of patients with AIDS, 13 (100%) of patients with ARC, 24 (69%) of 35 patients with LAS and 9 (39%) of 23 asymptomatic homosexuals were sero-positive. Heterosexual controls were negative. All IF-positive sera tested by Western blot contained antibodies against specific viral proteins. High titers (greater than or equal to 1:1280) of serum antibodies against LAV/HTLV-III virus were detected in 71% of AIDS patients, 62% with ARC, 38% LAS and 13% among asymptomatic homosexuals. Our data show that the presence of LAV/HTLV-III antibodies correlates with the presence of infectious virus. Antibody titers may also correlate with progression toward AIDS.
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PMID:Prevalence of AIDS-associated retrovirus and antibodies among male homosexuals at risk for AIDS in Greenwich Village. 608 26

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

Infectious retroviruses have been detected in 22 of 45 randomly selected patients with acquired immune deficiency syndrome (AIDS) and in other individuals from San Francisco. The AIDS-associated retroviruses (ARV) studied in detail had a type D morphology, Mg2+-dependent reverse transcriptase, and cytopathic effects on lymphocytes. The viruses can be propagated in an established adult human T cell line, HUT-78. They cross-react with antiserum to the lymphadenopathy-associated retrovirus isolated from AIDS patients in France. Antibodies to ARV were found in all 86 AIDS patients and in a high percentage of 88 other homosexual men in San Francisco. This observation indicates the widespread presence of these lymphocytopathic retroviruses and their close association with AIDS.
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PMID:Isolation of lymphocytopathic retroviruses from San Francisco patients with AIDS. 620 63

Lymphadenopathy associated virus ( LAV ) has been isolated from patients with the acquired immunodeficiency syndrome (AIDS) or lymphadenopathy syndrome. Since the immune deficiency in AIDS seems to be primarily related to the defect of the helper-inducer T lymphocyte subset, the possibility that LAV is selectively tropic for this subset was investigated. Fractionation of T lymphocytes was achieved by cellular affinity chromatography with monoclonal antibodies. In a hemophilic patient who was a healthy carrier of LAV , reverse transcriptase activity and virus particles detected by electron microscopy were found only in cultures of helper-inducer lymphocytes. When infected with LAV in vitro, lymphocyte subsets from normal individuals yielded similar results. Virus production was associated with impaired proliferation, modulation of T3-T4 cell markers, and the appearance of cytopathic effects. The results provide evidence for the involvement of LAV in AIDS.
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PMID:Selective tropism of lymphadenopathy associated virus (LAV) for helper-inducer T lymphocytes. 632 60

In 1987, under the aegis of the governmental campaign against AIDS, military hospitals in Moscow established a department for the diagnosis and treatment of HIV-infected and AIDS patients among the military and their families. Clinical and laboratory examinations showed that 96 people out of 130 examined either were positive for HIV or were suffering from symptoms of AIDS. 77 were military from African countries, 15 from Russia, and 4 were their family members. Out of these 15 patients from Russia, 8 had been infected via sexual intercourse: 1 via homosexual and 7 via heterosexual intercourse. In 10 patients, HIV infection had been diagnosed 1-2 years after being infected, in 3 patients 3-6 years later, and in 2 patients more than 10 years afterwards. Every other patient exhibited symptoms of the second stage of AIDS: persistent generalized lymphadenopathy. 4 patients had lost body weight, 8 patients had prolonged fever, 2 had diarrhea, 4 had various dermatological symptoms, 4 had opportunistic infections, 5 had other infections (viral hepatitis, acute pneumonia, and salmonella), and 3 patients had other ailments (paranephritis, salpingoophoritis, endometritis, purulent otitis). The cases of 3 patients are described in detail. 4 out of 5 patients who were transferred to this special department demonstrated severe inflammatory processes as a consequence of their HIV-infection: paranephritis, pneumonia, purulent cholangitis, and salmonella. All patients also evinced damage to their immune system: the reduction of T-lymphocyte count and T-helper cells and the reduction of the index of T-helper/T-suppressor cells (to 0.31 from the norm of 1.1-2.2). The treatment of AIDS patients consisted of the use of azidothimidine, which inhibits the activity of reverse transcriptase; the stimulation of the immune system by means of timalin (10 mg for 5 days im); and treating secondary fungal infections (up to 8 million IU of nystatin/day, up to 4 million IU of levorin, and up to 200 mg of diflucan).
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PMID:[HIV infection in servicemen (the work experience of a specialized hospital department)]. 757 95

We diagnosed a patient with chronic myelogenous leukemia (CML) in chronic phase (CP) on the basis of clinical findings, Ph1 chromosome detected by cytogenetic analysis, and bcr-abl fusion mRNA detected by reverse transcriptase-dependent polymerase chain reaction (RT-PCR). One month after diagnosis, the patient developed extramedullary blast crisis in the lymph nodes, and then medullary blast crisis in the bone marrow, in which different surface markers were shown. Combination chemotherapy with BH-AC, VP16, and mitoxantrone was administered; this resulted in rapid disappearance of the lymphadenopathy, restoration of normal hematopoiesis, and no Ph1 chromosome being detected by cytogenetic analysis. RT-PCR performed to detect the residual Ph1 clone revealed that although the Ph1 clone was preferentially suppressed, it was still residual. The intensive chemotherapy regimen preferentially suppressed the Ph1-positive clone and led to both clinical and cytogenetic remission in this patient with BC of CML; we suggest that RT-PCR is a sensitive and useful method for detecting minimal residual disease during the clinical course of this disease.
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PMID:Disappearance of Ph1 chromosome with intensive chemotherapy and detection of minimal residual disease by polymerase chain reaction in a patient with blast crisis of chronic myelogenous leukemia. 836 86

In order to determine the genotypic maturation status of the proliferating lymphoid cells in angioimmunoblastic lymphadenopathy (AILD) and in anaplastic large cell lymphoma of T-type (T-ALC), recombinase activating gene (RAG-1 and RAG-2) expression was assessed in six AILD and five T-ALC cases using a sensitive reverse transcriptase (RT) and competitive (C) polymerase chain reaction (PCR). RAG transcripts were not detectable in nine cases with high proliferating activity, suggesting that in most cases the proliferating cells are derived from mature (rearranged) lymphocytes. However, low levels of RAG transcripts were detected in one AILD and one T-ALC case and are consistent with either an involvement of immature lymphoid precursors in the proliferating pool or a deregulated T-cell maturation pathway with persistence of RAG expression. An association between RAG gene expression and poor response to therapy is possible but has to be tested in larger prospective series.
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PMID:Expression of human recombination activating genes (RAG-1 and RAG-2) in angioimmunoblastic lymphadenopathy and anaplastic large cell lymphoma of T-type. 851 81

A new antiretroviral agent, 2'-beta-fluoro-2',3'-dideoxyadenosine (FddA), is an acid-stable compound whose triphosphate form is a potent reverse transcriptase inhibitor with in vitro anti-human immunodeficiency virus (HIV) activity and a favorable pharmacokinetic profile. Severe combined immunodeficiency (SCID) mice reconstituted with human peripheral blood leukocytes (hu-PBL-SCID mice) provide a useful small-animal model for HIV research. In the present study we utilized this experimental system for the in vivo evaluation of the anti-HIV activity of this new compound when administered prior to infection. Initial studies revealed that, following a challenge with 50 100% tissue culture infective doses of HIV type 1 lymphadenopathy-associated virus, 39 of 42 (93%) control mice developed HIV infection, as evidenced by positive coculture or positive PCR. Administration of zidovudine decreased the infection rate to 5 of 16 (31%), while administration of FddA decreased the infection rate to 0 of 44 (0%). In follow-up controlled studies, the anti-HIV activity of FddA was confirmed, with 18 of 20 control mice showing evidence of HIV infection, compared with 4 of 20 FddA-treated mice. In addition to having direct anti-HIV effects, FddA was found to have a protective effect on human CD4+ T cells in the face of HIV infection. Mice treated with FddA were found to have a significantly higher percentage of CD4+ T cells than controls (10.3% +/- 3.4% versus 0.27% +/- 0.21%; P = 0.01). Thus, FddA, with its potent anti-HIV activity in vivo, high oral bioavailability, long intracellular half-life, and ability to preserve CD4+ cells in the presence of HIV, appears to be a promising agent for clinical investigation.
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PMID:Potent activity of 2'-beta-fluoro-2',3'-dideoxyadenosine against human immunodeficiency virus type 1 infection in hu-PBL-SCID mice. 889 Nov 46

Bovine immunodeficiency-like virus (BIV) was first isolated from an animal showing transient leucocytosis, lymphadenopathy, lesions in the central nervous system and progressive weakness and emaciation. Similar signs are observed in other immunosuppressive lentiviral infections. BIV, like other lentiviruses, has been isolated from peripheral blood mononuclear cells and lymphoid tissue of infected animals. However, the in vivo cellular tropism of BIV remains unclear although initial studies indicate that BIV may be pantropic, infecting T cells, B cells and monocytes similar to some of the immunodeficiency-causing lentiviruses. PCR, Southern blot hybridisation, cell culture and reverse transcriptase assays were used to demonstrate the presence of BIV proviral DNA and the production of infectious virus in CD2+, WC1+, B cells and monocytes during the acute stages of infection. Western immunoblot assays were used to assess the development of antibody responses towards the virus.
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PMID:Investigation of the cellular tropism of bovine immunodeficiency-like virus. 976 70


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