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Query: UMLS:C0019693 (HIV)
170,526 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Using flow cytometry, monoclonal antibodies to the HIV proteins p24, gp41 and p17 were evaluated for their ability to detect HIV antigens associated with HIV-infected T cells. Mixtures containing varying ratios of HIV-infected and uninfected cells were subjected to analysis with these monoclonal antibodies. In most cases, the monoclonal antibodies identified the correct ratio of HIV-infected cells to uninfected cells in the mixtures tested. An HIV anti-p24 monoclonal antibody was selected for further studies. Flow cytometric analysis was performed on various populations of cells including uninfected, acutely infected and chronically infected cells. Based on cell population fluorescence intensity three distinct regions were identified. In the first region were cells having low level fluorescence that were considered negative for HIV antigens, a profile detected in uninfected cells, and in the majority of cells in the first days following acute HIV infection. In the second region were those cells exhibiting strong fluorescence such as chronically infected cells or acutely infected cells several days after infection. A third region was identified containing cells that were intermediate in fluorescence intensity. Cells exhibiting intermediate intensity fluorescence appeared to have low concentrations of HIV p24 antigen associated with them either through viral adsorption and uptake or through low level virus expression. These intermediate region cells appeared in the early stages following acute infection, and also when chronically infected cells and uninfected cells were permeabilized together, suggesting a 'leaching' of HIV proteins from highly infected cells to uninfected cells. This leaching type of phenomenon could present problems in determining gating parameters for positive cells since uninfected cells that have associated HIV antigens exhibit higher fluorescence intensity than uninfected cells.
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PMID:Evaluation of a flow cytometric model for monitoring HIV antigen expression in vitro. 164 Jan 8

A panel of highly purified synthetic oligopeptides representing defined parts of the gag and env proteins of HIV-1 and HIV-2 were used as antigens in ELISA for serodiagnosis of HIV-1 and HIV-2 infection. The analysis included sera from 321 HIV-infected patients and 201 healthy controls from the Ivory Coast, where the prevalence is high for both HIV-1 and HIV-2, and sera from European HIV-1-infected individuals. All sera from HIV-1-infected individuals reacted with a 20 amino acid (a.a.) peptide JB-4c (a.a. 594-613) derived from a highly immunogenic conserved region of the external part of gp41. An equally good response was seen in the HIV-2-infected individuals to a 20 a.a. peptide, JB-16c, from the corresponding part of HIV-2 gp36. Both HIV-1- and HIV-2-seropositive individuals responded well to a peptide, JB-8pc (a.a. 427-448), representing the C-terminal end of the putative CD4-binding site of gp120 of HIV-1. The frequency of reactivity to three selected HIV-1 gag peptides derived from p17 and p15 was 60-70% in both HIV-1 and HIV-2-positive sera. To distinguish between HIV-1 and HIV-2 infection, the sera were titrated against the peptides. Although there was a high degree of cross-reactivity at lower serum dilutions, it was possible to discriminate the infections at higher dilutions to the HIV-1 and HIV-2 gp41/gp36 peptides JB-4c and JB-16c. Analysis of serum reactivity to several selected peptides thus allowed the identification of HIV infection, and the discrimination between HIV-1 and HIV-2.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Specific synthetic peptides for detection of and discrimination between HIV-1 and HIV-2 infection. 167 44

The gag and pol genes of the human immunodeficiency virus type 1 (HIV-1) (ref. 1) are translated as two polyproteins, Pr55gag and Pr160gag-pol (refs 2-6), which are subsequently cleaved by the action of a virus-encoded protease into the four structural gag proteins of the virion core (p17, p24, p7 and p6) and the pol-encoded enzymes essential for retrovirus replication (protease, reverse transcriptase, ribonuclease H, and endonuclease). Mutational inactivation of the proteases of HIV-1 and other retroviruses results in immature, non-infectious virions, indicating that exogenous inhibition of the protease may represent an attractive approach to anti-AIDS therapy. Here we demonstrate that synthetic peptide analogues, which are potent inhibitors of purified HIV-1 protease, inhibit the processing of the viral polyproteins in cultures of HIV-1-infected T lymphocytes and attenuate viral infectivity.
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PMID:Inhibition of HIV-1 protease in infected T-lymphocytes by synthetic peptide analogues. 168 46

Two monoclonal antibodies (MAbs) against p27 and one against p17 of simian immunodeficiency virus (SIV) from rhesus macaques were produced and characterized by reacting with disrupted, viral antigens on immunoblots. Human immunodeficiency virus type 1 (HIV-1), HIV-2 and SIV isolates from sooty mangabey, stump-tailed macaque, rhesus macaque and African green monkey (SIVSM, SIVStM, SIVMAC and SIVAGM) were used for comparative analysis. The p27 monoclonal antibodies HE3 and FA2 reacted with SIVMAC and SIVSM, but not with HIV-1, HIV-2, SIVStM and SIVAGM. The p17 monoclonal antibodies reacted with SIVMAC and SIVStM, but not HIV-1, HIV-2, SIVSM and SIVAGM. The differential reactivity of these monoclonal antibodies indicated that common conserved antigenic epitopes are shared between SIVMAC and SIVSM with respect to p27 MAbs and between SIVMAC and SIVStM with respect to p17. Since these MAbs reacted differently with the SIV isolates, they are useful reagents for comparative pathogenesis studies for differentiating SIV isolates.
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PMID:Characterization of monoclonal antibodies that distinguish simian immunodeficiency virus isolates from each other and from human immunodeficiency virus types 1 and 2. 168 69

Retroviruses encode proteinases necessary for the proteolytic processing of the viral gag and gag-pol precursor proteins. These enzymes have been shown to be structurally and functionally related to aspartyl proteinases such as pepsin and renin. Cerulenin is a naturally occurring antibiotic, commonly used as an inhibitor of fatty acid synthesis. Cerulenin has been observed to inhibit production of Rous sarcoma virus and murine leukaemia virus by infected cells, possibly by interfering with proteolytic processing of viral precursor proteins. We show here that cerulenin inhibits the action of the HIV-1 proteinase in vitro, using 3 substrates: a synthetic heptapeptide (SQNYPIV) which corresponds to the sequence at the HIV-1 gag p17/p24 junction, a bacterially expressed gag precursor, and purified 66 kDa reverse transcriptase. Inhibition of cleavage by HIV-1 proteinase required preincubation with cerulenin. Cerulenin also inactivates endothiapepsin, a well-characterised fungal aspartyl proteinase, suggesting that the action of cerulenin is a function of the common active site structure of the retroviral and aspartic proteinases. Molecular modelling suggests that cerulenin possesses several of the necessary structural features of an inhibitor of aspartyl proteinases and retroviral proteinases. Although cerulenin itself is cytotoxic and inappropriate for clinical use, it may provide leads for the rational design of inhibitors of the HIV proteinase which could have application in the chemotherapy of AIDS.
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PMID:In vitro inhibition of HIV-1 proteinase by cerulenin. 169 Jan 52

A thirty amino acid synthetic peptide (HGP30) representing the conserved region of HIV-1 p17 induced high titer antibodies to the native p17 in rabbits. This immune sera neutralized HIV-1 replication in cell culture and one of the high titer antisera also inhibited CD4-dependent cell fusion. Pepscan analysis with overlapping nonapeptides derived from the sequence of HIV-1 p17 identified the sequence (KE) ALDKIEE (EQ) as the major antibody binding site. Sera of 9% of AIDS patients (7/76) and 18% of HIV-1 seropositive healthy homosexuals (40/223) were positive for HGP30 antibodies. Decline in HIV-1 p17 antibodies has been shown to be related to disease progression in both children and adults, suggesting that HIV-1 p17 antibodies may be protective. Hence, a synthetic HIV-1 p17 peptide, representing the immunodominant epitope, could be useful as a candidate vaccine for immunization of HIV-1 seronegative or seropositive healthy homosexuals.
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PMID:Immune response and epitope mapping of a candidate HIV-1 p17 vaccine HGP30. 169 Feb 77

We have succeeded in infecting human thymic lymphocytes with both the HIV-IIIB laboratory strain of HIV-1 as well as with a clinical isolate of this virus. Thymic lymphocytes were at least as susceptible to infection by HIV-1 as were cord blood lymphocytes, but appeared to display somewhat greater resistance to the cytopathic effects of the virus. As measured variously by each of indirect immunofluorescence for detection of viral p17, antigen capture assay for the presence of viral p24 in culture fluids, and levels of viral reverse transcriptase activity in culture fluids, infection of thymic lymphocytes could be detected as early as 2 days after infection by HIV-1, and persisted through at least 14 days of tissue culture maintenance. These findings suggest that thymic lymphocytes may be susceptible to infection by HIV-1 in vivo, and may also be relevant to our understanding of HIV-1-induced pathogenesis, particularly in pediatric populations.
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PMID:Infection of human thymic lymphocytes by HIV-1. 169 Feb 86

Five mouse hybridomas which produce monoclonal antibodies against the p17 core protein of HIV-1 have been isolated. Cross-competition assays and mapping with synthetic peptides demonstrate that two closely related epitopes are identified by these antibodies. Directed against two neighbouring peptides at the carboxy-terminal end of the molecule, they can be used for the selective detection of p17 polypeptide in a viral extract or in an infected cell lysate by a solid-phase sandwich enzyme immunoassay.
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PMID:Characterization of monoclonal antibodies against the p17 core protein of the human immunodeficiency virus 1. 169 Dec 36

The reverse transcriptase enzyme of HIV-1 is known to be error-prone. We were interested in the possibility of isolating a variant HIV-1 strain that might be capable of replication in the presence of AZT, thought to act by antagonizing reverse transcriptase activity. Toward this end, chronically infected H-9 cells were exposed to various concentrations of AZT for at least 500 days. No mutant has yet arisen from such cultures, which continued to produce high levels of each of the viral proteins p24, p17, gp41, and gp51/66 in the presence of the drug. Notwithstanding such expression of viral antigens, culture fluids from these various AZT-treated cultures were not capable of infecting otherwise susceptible target cells. Electron microscopic observations of AZT-treated chronically infected H-9 cells indicated a lower production of viral structures, in comparison with control cultures. Furthermore, those particles seen at the plasma membrane of AZT-treated cells often appeared to be envelope-deficient. These data suggest that AZT may be able to interfere in some way with proper assembly and/or packaging of infectious progeny HIV-1 at the cell membrane, although other modes of action for a postintegrational effect of AZT cannot be excluded.
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PMID:AZT (zidovudine) may act postintegrationally to inhibit generation of HIV-1 progeny virus in chronically infected cells. 169 85

Immune response to HIV infection is generally characterized by appearance of antibodies to the gag protein p24 early in infection, and by apparent loss of p24 antibodies accompanied by increases in p24 antigen levels with disease progression. Precise definition of the immunodominant epitopes present in gag gene proteins has potential clinical significance. Seventeen anti-gag monoclonal antibodies (MAb) were used in enzyme-linked immunosorbent assays (ELISA) with antigens expressed by nine recombinant clones to define epitopes on HIV gag proteins which elicit an immune response. All of the MAbs tested, except two anti-p17, reacted with a clone which expresses the carboxyl terminal 13 amino acids of p17 and all of p24 and p15. All anti-p24 MAbs reacted with clones containing all of p24. MAbs reacted differentially with clones containing deleted regions depending on the antigenic portion expressed. Of thirteen potential identifiably different genomic regions which could be predicted from the genomic structure of the clones, eight different antigen epitopes were defined: two on p17, five on p24, and one on p15 (in the region corresponding to the carboxyl terminal protein p6). Six regions did not appear to react with any of the monoclonal antibodies available. Identification of the epitopes present in the cloned antigens should allow their use to evaluate sera from HIV-infected donors at different clinical stages of progression to AIDS.
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PMID:Epitope mapping of the HIV-1 gag region by analysis of gag gene deletion fragments expressed in Escherichia coli defines eight antigenic determinants. 169 22


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