Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019693 (HIV)
 170,526 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Eleven murine hybridoma clones were selected for their ability to produce anti-HIV-1 integrase (IN) antibodies. Competition and epitope mapping studies allowed segregation of the monoclonal antibodies (MAbs) into four distinct classes. The five MAbs that comprise the first class showed high affinity for epitopes within an N-terminal domain of 58 amino acids that includes a conserved zinc finger motif. The second class, with two MAbs, showed high affinity for epitopes within 29 amino acids at the C terminus. Another two MAbs, which constitute the third class, displayed moderate affinities for epitopes that mapped to regions within the highly conserved catalytic core referred to as the D,D(35)E domain. One of these MAbs showed significant cross-reactivity with HIV-2 IN and weak, but detectable, cross-reactivity with RSV IN. The remaining two MAbs, which comprise the fourth class, exhibited fairly low binding affinities and appeared to recognize epitopes in the zinc finger motif domain as well as the C-terminal half of the IN protein. The MAbs can be used for immunoprecipitation and immunoblotting procedures as well as for purification of HIV-1 IN protein by affinity chromatography. We show that several can also be used to immunostain viral IN sequences in HIV-1-infected T cells, presumably as a component of Gag-Pol precursors. Finally, analysis of our mapping and competition data suggests a structure for mature IN in which the C terminus approaches the central core domain, and the N and C termini touch or are proximal to each other. These MAbs should prove useful for further analyses of the structure and function of IN both in vitro and in vivo.
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PMID:Monoclonal antibodies against HIV type 1 integrase: clues to molecular structure. 753 24

HIV-1 reverse transcriptase is a dimeric enzyme mainly involved in the replication of the viral genome. A filamentous phage cDNA expression library from human lymphocytes was used to select cellular proteins interacting with HIV-1 reverse transcriptase Affinity selections using the bacterially expressed monomeric large subunit of reverse transcriptase (p66) yielded host beta-actin. This clone was expressed as glutathione-S-transferase fusion protein which was identified by using a specific antibody against beta-actin. Furthermore we show that also the eukaryotic beta-actin binds to either the large subunit of reverse transcriptase or to the Pol precursor polyprotein in vitro. The reverse transcriptase/beta-actin interaction might be important for the secretion of HIV-1 virions.
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PMID:The large subunit of HIV-1 reverse transcriptase interacts with beta-actin. 753 22

The human immunodeficiency virus type-1 (HIV-1) integrase protein (IN) mediates the insertion of linear double-stranded viral DNA into the host genome. Mutations in IN can have different effects on the virus life cycle. In this study, Gag-Pol polyprotein processing, Tat synthesis, and viral replication were investigated in integrase-defective HIV-1 mutants. In the absence of IN synthesis, the Gag-Pol polyprotein stability, packaging, and/or processing was reduced. There was limited expression of Tat observed in IN mutants, but no viral replication.
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PMID:Analysis of human immunodeficiency virus type 1 integrase mutants. 749 94

An improved non-radioisotopic (Non-RI) reverse transcriptase (RT) assay with a template-primer-immobilized microtiter plate is described, which has greater sensitivity than the former Non-RI RT assay previously described. Non-RI and commercially available non-radioactive (Non-RA) RT assays were compared for their ability to detect various polymerases. Two RTs from Rous-associated virus 2 (RAV-2) and avian myeloblastosis virus (AMV), one polymerase from Escherichia coli (Pol-I) and one recombinant RT of human immunodeficiency virus type 1 (HIV-1) were assessed. Two HIV-1 samples in a culture supernatant and pelleted virion suspended in Triton X-100 solution were measured. The Non-RI RT assay was one hundred times more sensitive by RAV-2 and Pol-I polymerases, and one thousand times more sensitive by the Non-RA assay than by the AMV RT. The Non-RI RT assay was 10, 16 and 64 times more sensitive than the Non-RA assay for measuring recombinant HIV-1 RT, pelleted virus and virus suspended in culture medium, respectively. To explain the discrepancy, it is shown that free biotin, such as in culture medium, disturbs the assay system of the Non-RA RT assay, but not the Non-RI assay. The present assay can be used to clarify the inhibitory mechanism of an anti-HIV-1 substance.
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PMID:Comparable sensitivities for detection of HIV-1 reverse transcriptase (RT) and other polymerases by RT assays requiring no radioisotopic materials. 754 93

During replication of human immunodeficiency virus type 1 (HIV-1), proteolytic cleavage of Gag and Gag-Pol precursor proteins into different functional protein subunits is catalyzed by the viral proteinase, and this enzyme is the target of the antiviral proteinase inhibitor, Ro 31-8959. We investigated in vitro which HIV mutants with reduced sensitivity to Ro 31-8959 emerged during proteinase inhibition treatment; from three different HIV-1 strains, comparable progeny virus resistant to proteinase inhibitor were found, whereas the same experimental protocol detected no resistant HIV-2 mutants. Molecular analysis of the mutations underlying resistance revealed a multistep mechanism in which an amino acid exchange was common to all resistant isolates, and in all experiments preceded further exchanges at position 90 (leucine to methionine) and/or at position 54 (isoleucine to valine). For wild-type strains the 90% inhibitory concentrations of Ro 31-8959 were close to 20 nM, whereas HIV-1 mutants with all 3 amino acid exchanges had more than 50-fold increased 90% inhibitory concentrations (above 1000 nM). The primary event (Gly-48 to valine) occurs at the hinge of the flaps of the proteinase, thus hampering entry of the inhibitor to the active center and suggesting steric hindrance. Detailed knowledge of this stereotypic process could open inhibitor design, thus preventing conceivable escape of resistant virus on proteinase inhibitor action.
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PMID:Resistance of HIV type 1 to proteinase inhibitor Ro 31-8959. 757 26

In an attempt to analyse the role of anti-envelope immunity in the protection of rhesus monkeys against an HIV-2 intravenous challenge, rhesus macaques were immunized twice with recombinant HIV-2 ROD vaccinia viruses (10(8) p.f.u. each) at days 0 and 30, followed by booster injections of purified HIV-2 proteins at months 8, 9, 15 and 27. One group of five macaques was immunized with the Gag, Pol, Vif and Nef antigens, whereas a second group received the same antigens with the addition of HIV-2 Env protein. Eight months after the last boost, the animals were challenged by intravenous injection of 100 AID50 of a monkey PBMC-grown stock of HIV-2 SBL. None of the animals was protected in spite of high humoral immune responses on day of challenge as determined by ELISA and Western Blot assays.
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PMID:Heterologous HIV-2 challenge of rhesus monkeys immunized with recombinant vaccinia viruses and purified recombinant HIV-2 proteins. 762 17

Cytotoxic T lymphocytes (CTL) may play an important role in host defense against HIV-1 infection. In this study, we examined the responses of circulating effector CTL (CTLe) specific for Gag, Pol, Env, and Tat in 57 HIV-1-infected men, 49 of whom were asymptomatic and had documented time since seroconversion of < 8 years. CTLe responses to at least one of the four HIV-1 gene products were detected in 83% of the subjects. The magnitude and prevalence of the anti-Tat responses were significantly less than the responses to Gag, Pol, and Env. Cell depletion studies indicated that the lytic activity against the HIV-1 structural proteins was mediated by CD8+ T cells, although 30% of Env-specific lysis was mediated by CD16+ natural killer cells. Anti-HIV-1 CTLe responses against Gag and Pol were significantly less in subjects infected for over 6 years as compared to those infected for shorter periods of time. We found no correlation, however, between anti-HIV-1 CTLe responses and either CD4+ or CD8+ T cell counts, rates of CD4+ T cell loss, HIV-1 infectious viral load, use of antiviral medications, or subsequent progression to AIDS. Our results indicate that anti-HIV-1 CTLe activity is relatively stable in asymptomatic subjects infected < 6 years, and is not an early marker for risk of disease progression.
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PMID:Anti-HIV type 1 cytotoxic T lymphocyte effector activity and disease progression in the first 8 years of HIV type 1 infection of homosexual men. 763 63

Bronchoscopy was carried out in 32 HIV seropositive patients, most with AIDS during the period between January 1992 and August 1993. In 14 patients tuberculosis was diagnosed, in 13 it was bacteriologically confirmed. The mean age of the examined patients was 35.5 years (range 22-49 years). In 50% of the BAL samples bacterioscopy was positive. Bacteriological examination of the sputum and BAL fluid (bacterioscopy and culture) produced a confirmation of tuberculosis in 99.9% of the cases.
Pneumonol Alergol Pol 1995
PMID:[The role of bronchoscopy and bronchoalveolar lavage in diagnosis of pulmonary tuberculosis in AIDS]. 763 65

Lack of disease in long-term nonprogressors with human immunodeficiency virus type 1 (HIV-1) infection was strongly associated with very low copy numbers of HIV-1 DNA and RNA in peripheral blood mononuclear cells and plasma and the presence of high levels of anti-HIV-1 CD8+ memory cytotoxic T lymphocytes specific for Gag, Pol, and Env, compared with levels present in intermediate and advanced progressors. CD8+ memory cytotoxic T lymphocytes may have an important role in controlling HIV-1 replication and preventing disease in long-term nonprogressors.
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PMID:High levels of anti-human immunodeficiency virus type 1 (HIV-1) memory cytotoxic T-lymphocyte activity and low viral load are associated with lack of disease in HIV-1-infected long-term nonprogressors. 763 30

Over the past decade, with the use of plasma-derived factor VIII and factor IX, treated with virucidal methods, as well as with recombinant factor VIII, the replacement therapy of hemophilia has been intensified. In developed countries, a majority of patients are being treated at home, and large groups of children benefit from primary prophylaxis. A serious task in these countries for the coming years is the management of patients infected with HIV. In Poland and less-developed countries, the supply of antihemophilic factor concentrates is inadequate. Patients with inhibitor antibodies should be included in programmes of immune tolerance inducement. Many patients who had been multitransfused with cryoprecipate or received lyophilized concentrates before 1985, have developed chronic hepatitis associated with viral infections. About 15-30% show evidence of cirrhosis. Recombinant technologies should be improved and become more accessible in order to provide patients with safe and cheap antihemophilic factor concentrates. A true break-through in the hemophilia treatment would be a repair of the inherited clotting defect with gene therapy.
Acta Haematol Pol 1995
PMID:[Current status and future prospects of hemophilia treatment]. 765 34


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