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)

The construction and preliminary biological characterization of three molecular clones of human immunodeficiency virus type 1 (HIV-1) are reported: HIV-1LAI from a French man with AIDS, HIV-1MAL from a Zairian boy with ARC, and HIV-1ELI from a Zairian woman with AIDS. All three sequences were found to code for infectious viruses. Both the host range and the kinetics of infection in CD4+ cells were different for the three viruses. Virus derived from each molecular clone was infectious on peripheral blood mononuclear cells (PBMC), although LAI and ELI displayed more rapid growth kinetics than MAL. The viruses had different tropisms and growth kinetics in six cell lines. LAI was infectious in all of the cell lines and produced high levels of reverse transcriptase activity. MAL and ELI had more restricted tropisms: MAL could only replicate on SupT1, whereas ELI grew on Jurkat and MT-4, was delayed on CEM and H9, and was unable to infect U937 cells. In addition, we observed that both the replicative capacity and the cell tropism of viruses could change after passage through some established cell lines. These results suggest that the genotypes of some viruses in vitro are not stable and that selection for growth can cause the fairly rapid appearance of variants with increased growth potential.
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PMID:Changes in growth properties on passage in tissue culture of viruses derived from infectious molecular clones of HIV-1LAI, HIV-1MAL, and HIV-1ELI. 168 26

An oriental remedy, Sho-saiko-to (SST) consisting of a mixture of aqueous extracts from seven different plants and whose most active component is the chemically defined compound baicalein was tested for its ability to inhibit the production of the human immunodeficiency virus (HIV). The testing was done with cultures of human lymphocytes obtained from HIV-positive asymptomatic subjects and patients with ARC or AIDS. The replication of the virus was monitored by quantitative assay of the reverse transcriptase (RT) activity and of the synthesis of antigen p24. The lymphocyte cultures (LC) were maintained in the absence and in the presence of 25, 50 or 100 micrograms/ml of SST, and monitored for up to 5 weeks. The results showed that in LC from asymptomatic subjects RT activity and synthesis of p24 was completely inhibited by low concentrations of SST. High concentrations of SST inhibited virus replication in 80% of LC from ARC patients, but were completely ineffective in LC from AIDS patients. It was observed that the RT activity was more sensitive to inhibition by SST than the synthesis of p24, and that the antiviral effect was dependent on the virus load of the LC.
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PMID:Inhibition of HIV replication in lymphocyte cultures of virus-positive subjects in the presence of sho-saiko-to, an oriental plant extract. 170 25

The polysulfated polyxylan HOE/BAY946, which has been tested in two pilot studies in ARC/AIDS patients and in asymptomatic HIV carries in Germany, was believed to act by inhibiting virus attachment to the cell. However, the drug was also found to reduce the amount of HIV particles released from infected peripheral blood mononuclear cells (PBMC) in vitro. Furthermore, preincubation of PBMC with the drug led to a partial inhibition of a following HIV infection, suggesting that the drug also affects virus entry. Electron Paramagnetic Resonance (EPR) measurements on uninfected human lymphocytes using 5-proxyl-nonane as spin label demonstrated smaller hyperfine coupling constant (aN) values in the presence of HOE/BAY946 or dextran sulfate 5000. Accordingly, h-1p/h-1H ratios were decreased, indicating increased plasma membrane hydrophobicity and a membrane-stabilizing effect of the drugs. Culture of the chronically HIV-infected monocytic cell line U937/HIV-2D194 in the presence of HOE/BAY946 specifically and drastically reduced the release of virions and the intracellular synthesis of viral proteins as determined by radioimmunoprecipitation and reverse transcriptase assays. In conclusion, although the EPR studies showed a physico-chemical effect on membrane polarity, HOE/BAY946 and dextran sulfate clearly affect processes beyond the cell membrane. Thus, in contrast to previous reports suggesting that polysulfated sugars affect HIV only by inhibiting virus binding to uninfected cells, they clearly inhibit HIV in infected cells as well and appear to have a pleiotropic mode of action. Such drugs may be less likely to result in viral resistance after prolonged application than substances acting only on one step in the life cycle of the virus.
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PMID:Anti-human immunodeficiency virus (HIV) drug HOE/BAY946 increases membrane hydrophobicity of human lymphocytes and specifically suppresses HIV-protein synthesis. 196 49

LAV/HTLV-III/AAV viruses were isolated from 20 German patients with ARC/AIDS in order to investigate strain variation. Virus was isolated from the peripheral blood and/or cerebrospinal fluid (CSF) in umbilical cord peripheral blood lymphocyte (PBL) cultures. Isolates were identified by their cytopathic effect (CPE), by reverse transcriptase assays on cell-free infected culture supernatant fluid (SNF), and one or more of the following: immunofluorescence assays on infected cells for viral antigen using HTLV-III reference sera, Western blot analysis of cell-free infected culture SNF, electron microscopy of infected cells, and Southern blot restriction analysis and specific HTLV-III probing of DNA extracted from infected cultured PBL. The isolates could be classified into three groups according to differences in growth rate and cytopathic effect: Most showed what was regarded as the typical CPE, while some either grew rapidly and induced a striking CPE and others grew slowly with minimal CPE. In one patient, virus producing typical CPE was isolated from the peripheral blood while the isolate from his filtered cell-free CSF produced atypical slow CPE, suggesting that antigenic variation may occur with persistent infection or that superinfection may occur. Southern blot DNA restriction analysis of the DNA of three selected isolates showed that two of the isolates were similar but that the restriction pattern of all three differed from patterns previously published. Our results supplement the accumulating evidence of genetic variation among LAV/HTLV-III strains. The extent of this variation needs to be evaluated for any effect on the sensitivity of diagnostic tests, on the strategy of vaccine development, on tissue tropism by altering the viral surface receptor-binding sites, and possibly on the development of specific chemotherapy.
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PMID:Isolation of variants of lymphocytopathic retroviruses from the peripheral blood and cerebrospinal fluid of patients with ARC or AIDS. 242 49

Isolation of Human Immunodeficiency Virus (HIV) was attempted from the tears of seven patients with ARC. For two of these patients the fluid from cell cultures showed significant reverse transcriptase activity. One strain was maintained on C.E.M. (T lymphocytes cell line). Indirect fixed cell immuno fluorescence and Western Blot tests have shown this strain to be a HIV. This result confirms other already published data. Although there is no evidence of transmission through tears, the presence of the virus should not be forgotten.
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PMID:[Isolation of LAV/HTLV III from tears of patients with the ARC syndrome]. 244 Sep 38

The Fairfield Hospital experience with isolation of HIV from peripheral blood leucocytes, cerebrospinal fluid and semen is described. To date HIV has been isolated from single specimens of blood from 45% of patients with AIDS, 35% of patients with lymphadenopathy syndrome AIDS-related complex or ARC and 14% of asymptomatic antibody positive individuals. HIV was recovered from peripheral blood leucocytes in the presence of phytohemagglutinin and interleukin-2. The presence of virus in the supernatant fluid was detected using reverse transcriptase and immunofluorescence assays. Supernatants with borderline activity were confirmed by infection of a continuous cell line.
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PMID:Isolation of HIV from Australian patients with AIDS, AIDS related conditions and healthy antibody positive individuals. 245 95

The 1st isolation of HIV in Israel is recorded in the report. Out of 11 homosexual men with antibodies to HIV, the virus was found in 7 of the men. In addition, the virus was found in a seropositive woman with ARC who was the wife of a bisexual patient. The isolation of HIV appeared more efficient in ARC or LAS patients. Isolation of HIV is done through cocultivation of the patient's peripheral lymphocytes with HUT-78 cells or with phytohemagglutinin-stimulated normal cord blood lymphocytes. Because of the unique characteristics of HIV, a reverse transcriptase activity, cytopathic effects on target T-lymphocyte and syncytium of giant and multinucleated cells, identification of the virus was based on the detection of these qualities. HIV antibodies located by immunoassays and immunofluorescence. The virus was isolated in 50% of the AIDS patients, 85% of ARC patients and 60% of LAS patients. Knowing the characters of currently isolated strains of HIV will help researchers to understand the initial stages and movement of the disease through Israel and help them develop steps towards its control.
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PMID:Isolation of HIV from Israeli patients and asymptomatic carriers. 245 84

Azidothymidine is a new antiviral drug that acts by competitive inhibition of reverse transcriptase of retroviruses. Azidothymidine is now widely used in treatment of patients with AIDS or ARC; the most important side effects of this drug are anaemia and neutropenia. Recently pigmentary changes of the nails (diffuse pigmentation and longitudinal or transverse bands) provoked by azidothymidine-treatment have also been reported. We describe a such case.
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PMID:[Nail pigmentation caused by azidothymidine]. 280 86

A new case of lymphocytic interstitial pneumonitis developed in the course of a persistent generalized lymphadenopathy syndrome is reported. The patient was a 30-year old Haitian woman with only her ethnic risk factor. Broncho-alveolar lavage showed high cellularity with mostly major lymphocytosis (76%) and a fall of the OK T4/OK T8 ratio to 0.23. The LAV was isolated from the lavage fluid lymphocytes on the same day and within the same culture time as from blood, using lymphocyte culture and measurement of reverse transcriptase activity in the supernatant fluid of cell cultures. This, together with the strongly positive (1/80) LAV serology in fluid as compared with blood (1/640), suggested that the LAV virus was directly or indirectly involved in the pneumonitis, being responsible for lymphocyte proliferation as it is in lymph nodes. No superinfection with a bacterial, fungal or other than LAV viral agent was found in blood or in lavage fluid. Lymphocytic interstitial pneumonitis is uncommon in AIDS or ARC (13 cases reported), but its incidence no doubt is underestimated, as it may be latent. It certainly accounts for the high lymphocyte count observed in broncho-alveolar lavage fluid in the absence of superinfection and, most probably, for many cases of so-called "non-specific pneumonia". In 1986, patients with apparently primary lymphocytic interstitial pneumonitis should be investigated for AIDS or ARC.
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PMID:[Lymphocytic interstitial pneumopathy in AIDS-related complex. Presence of the LAV virus in the bronchoalveolar lavage fluid]. 294 80

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


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