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

Lymphocytes or lymphoblastoid cells that have been infected by HIV in vitro or exposed to its envelope glycoprotein (gp120) show abnormal inositol polyphosphate-mediated signal transduction and associated defects in calcium regulation. Such cells behave as though they were chronically activated and fail to respond to further activating signals. We now show that similar changes are seen in lymphocytes obtained from HIV-infected subjects at various stages of infection, despite the fact that only a minority of such cells are infected. Furthermore, the defect in the phosphatidylinositol hydrolysis pathway in lymphocytes obtained from AIDS patients reverses after treatment with zidovudine, in parallel with improvements in phytohaemagglutinin-induced proliferative response and interferon-gamma production.
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PMID:Lymphocytes from HIV-infected individuals show aberrant inositol polyphosphate metabolism which reverses after zidovudine therapy. 167 83

The ultimate consequence of infection with HIV is profound immunosuppression that is the result of both quantitative and qualitative abnormalities of the helper/inducer subset of T lymphocytes. The initial pathogenic event in HIV infection is binding of the envelope glycoprotein of HIV to the CD4 receptor molecule present on the surface of CD4+ T lymphocytes and monocyte/macrophages. In vivo the reservoir for HIV infection in the peripheral blood is the CD4+ T cell, whereas in other tissues the monocyte/macrophage may play a substantial role. As disease progresses in HIV-infected individuals, the viral burden in the peripheral blood CD4+ T cells increases. An understanding of the mechanisms involved in the transition from an initially low viral burden during the asymptomatic phase of HIV infection to the higher levels of virus expression detected in late stage disease is being investigated intensively. A number of potential agents that may influence regulation of HIV expression have been identified including mitogens, antigens, heterologous viruses, cytokines, and physical factors. The pathogenic mechanisms of HIV-induced neurologic abnormalities and the potential role of HIV in a number of other clinical manifestations of HIV infection are also discussed.
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PMID:Immunopathogenesis of HIV infection. 167 89

It has been previously demonstrated that the HIV envelope glycoprotein gp160 can inhibit the activation of T cells triggered by phytohemagglutinin, anti-CD3 antibody and Ag, caused in part by the modulation of the expression of CD4. In this study, we show that gp160 is also able to inhibit the Ag-independent adhesion of CD4+ T cells to B cells as anti-CD4 antibodies do. In addition, synthetic peptides (14 to 21 mer) derived from the gp160 sequence and analogous to the putative binding site of gp160 to CD4 (residues 418-460), and also covering residues 460 to 474 inhibit the capacity of both CD4+ T cell proliferation induced by tuberculin and anti-CD3 antibody and adhesion. This was not associated with inhibition of Ca2+ flux in T cell activation. These inhibitory activities are specific because a) CD4+ T cells but not CD8+ T cells are susceptible to their effects, and b) soluble CD4 neutralizes the inhibitory activities. Peptides are, however, about 100- to 1000-fold less potent inhibitors than the native gp160. In addition, they do not induce CD4 modulation. It is thought therefore that at least part of the gp160 inhibitory activity is not secondary to CD4 modulation but may rely either upon steric hindrance of CD4-MHC class II interaction, of CD4/CD3 TCR complex interaction, or upon negative signaling through binding to CD4. The latter hypothesis is suggested by the inhibition by gp160, gp160-derived peptides, and anti-CD4 antibodies of the Ag-independent adhesion of CD4+ T cells. This adhesion process has been previously shown to be mediated by the LFA-1 and CD2 molecules and not by the TCR/CD3 complex and by CD4. Together, these results support the role of part of the 418-460 region of gp160 as a binding site to CD4, and suggest that binding of part of this region to CD4 can alter T cell proliferation and adhesion. It is proposed that these effects are mainly mediated by negative signaling through CD4.
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PMID:Inhibition of CD4+ T cell activation and adhesion by peptides derived from the gp160. 167 23

A novel membrane-bound serine esterase in cultured human T4+ lymphocytes, recently purified and named tryptase TL2, binds specifically to the external envelope protein gp 120 of HIV-1, interacting with its V3 domain. This binding was selectively blocked by inhibitors of tryptase TL2 with a GPCR sequence in their reactive site, synthetic peptides corresponding with the sequences of the V3 domains of various HIV-1 strains with the GPGR sequence, and antibody against tryptase TL2, or neutralizing antibody against the V3 domain of HTLV-IIIB. These findings suggest that tryptase TL2 is a binding protein of the V3 domain of HIV-1 envelope glycoprotein.
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PMID:Tryptase TL2 in the membrane of human T4+ lymphocytes is a novel binding protein of the V3 domain of HIV-1 envelope glycoprotein gp 120. 167 98

The effect of carbohydrate structures on the adsorption of HIV-1 or of recombinant envelope glycoprotein gp 160 (rgp 160) to cells of the CEM line was investigated with an indirect immunofluorescence assay using gp 120-specific mouse monoclonal antibodies (mAbs) directed to envelope gp 120. The beta-D-galactosyl, alpha-D-mannosyl, beta-D-glucosyl, N-acetyl-beta-D-glucosaminyl, sialosyl, and L-fucosyl derivatives tested had no effect on this binding. However, preincubation of HIV-1 (or rgp 160) with the neoglycoprotein, beta-D-GlcNAc47-BSA, specifically inhibited the labeling, by some of the mAb used, of HIV-1 (or rgp 160) bound at the cell membrane. This inhibition occurred only with mAbs that were specific for the immunodominant "neutralizing" third variable region (V3) of gp 120. Competition for the binding to rgp 160 between beta-D-GlcNAc47-BSA and mAb was further demonstrated by use of affinity matrices substituted with one of the relevant mAb (110-4), or with beta-D-GlcNAc47-BSA. Besides beta-D-GlcNAc47-BSA-Sepharose, rgp 160 also bound with low affinity, but high specificity, to two other N-acetyl-beta-D-glucosaminyl affinity matrices, beta-D-GlcNAc-divinylsulfone-agarose and asialoagalactothyroglobulin-agarose. Conversely, beta-D-[125I]GlcNAc47-BSA bound specifically to gp 160-Sepharose. These results indicated that rgp 160 behaves as a N-acetyl-beta-D-glucosaminyl-binding protein for GlcNAc residues presented at high density on a carrier, the carbohydrate-binding site of which is close to, or located on the V3 region of gp 120.
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PMID:N-Acetyl-beta-D-glucosaminyl-binding properties of the envelope glycoprotein of human immunodeficiency virus type 1. 168 45

A novel membrane-bound serine esterase, named tryptase TL2, which is immunologically reactive with the antibody inhibiting induction of syncytia by human immunodeficiency virus-1 (HIV-1) (HATTORI, T., KOITO, A., TAKATSUKI, K., KIDO, H., and KATUNUMA, N., 1989, FEBS Lett., 248, 48-52), has been purified from a human T4+ lymphocyte clone. The enzyme has a molecular mass of 198 +/- 15 kDa, and is composed of two subunits of 32 kDa and four subunits of 28 kDa. The enzyme was strongly inhibited by the envelope glycoprotein gp120 of HIV-1, by synthetic peptides of V3 domains of gp120 s with the sequence GPGR in their center, which correspond to the principal neutralizing epitopes of the gp120s of various HIV-1 strains, by Kunitz-type inhibitors with the sequence GPCR in their active site, such as trypstatin, H130, and [Arg15, Glu52] aprotinin and by the microbial inhibitors leupeptin and antipain. This enzyme was specifically bound to the inhibitor V3 domain of gp120 of HIV-1, and this binding was blocked by the inhibitors of tryptase TL2, with a central motif GPCR or GPGR sequence in their center, but not by leupeptin and antipain without the motif. These findings suggest that tryptase TL2 is important in target site recognition and binding of HIV-1 in co-operation with CD4 receptor in the initial process of HIV-1 infection.
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PMID:A novel membrane-bound serine esterase in human T4(+)-lymphocytes is a binding protein of envelope glycoprotein gp120 of HIV-1. 168 71

The transmission of HIV requires the interaction of the cell-surface CD4 receptor and the viral envelope glycoprotein. Experiments were performed to determine the role of other cell-surface molecules in the development of HIV-induced syncytia. Although CEM and MT-2 cells had similar cell-surface CD4 receptor densities, less than 1% of CEM cells and greater than 95% of MT-2 cells formed syncytia with H9 cells chronically infected with HIV-1 (H9-IIIB). When compared with CEM cells, MT-2 cells exhibited a 10-fold and threefold greater capacity to form homotypic and heterotypic conjugates with H9 cells, respectively. Increasing the conjugate formation capacity of CEM cells with the lectin wheat germ agglutinin led to a greater than 30-fold increase in the formation of syncytia with H9/IIIB cells. The formation of syncytia between MT-2 and H9/IIIB cells was magnesium-, energy-, temperature-, and actin-cytoskeleton-dependent, and could be inhibited (65%) by an anti-LFA-1 monoclonal antibody. The combination of anti-leukocyte function-associated antigen-1 (LFA-1) and anti-CD2 monoclonal antibodies resulted in a synergistic inhibition (89%) of syncytium formation. These results indicate that integrins and other cell-surface adhesion molecules regulate HIV-induced syncytium formation.
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PMID:HIV-induced syncytium formation requires the formation of conjugates between virus-infected and uninfected T-cells in vitro. 168 45

The first step in infection of human mononuclear cells with HIV involves the high affinity binding of the viral envelope glycoprotein, gp120, to the cell-surface receptor, CD4. To gain a better understanding of the molecular basis of this interaction, we have analyzed the ability of gp120 to bind to a panel of 40 mutant CD4 proteins containing single or double amino acid substitutions. In addition, the binding of several anti-CD4 mAb to the mutant CD4 proteins was measured. These mAb were chosen on the basis of the previous demonstration that they bind to epitopes in CD4 adjacent to the gp120-binding site. This analysis permits discrimination between mutations that probably cause localized conformational changes and those that alter residues likely to make direct contact with gp120 and with the mAb. Our results indicate that gp120 from two different strains of HIV binds to a larger region of the CD4 protein than previously described. The data has also been used to map the epitopes of mAb previously identified as anti-idiotype vaccine candidates. The results have important implications for the development of CD4-based therapies for AIDS.
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PMID:Analysis of the site in CD4 that binds to the HIV envelope glycoprotein. 169 Dec 26

A human Epstein-Barr virus-transformed lymphoblastoid B-cell line was generated from peripheral blood mononuclear cells (PBMC) of an asymptomatic human immunodeficiency virus type I (HIV-1) seropositive donor, which produces a human monoclonal antibody K14 (IgG1), reactive with an epitope on the transmembrane part (gp41) of the envelope glycoprotein of HIV-1. This monoclonal antibody reacts with a lysate of HIV-1-infected H9 cells, gradient purified HIV-1, and a vaccinia recombinant HIV-1 gp160 protein, but not with HIV-2 antigens in an enzyme-linked immunosorbent assay (ELISA). When used as an immobilized ligand in an immune affinity column, K14 selectively purifies gp41 from a HIV-1-infected H9 cell lysate. Although no reactivity was observed in ELISA with a panel of partially overlapping synthetic nonapeptides spanning the whole length of HIV-1 gp41, it was shown to react with recombinant envelope proteins, provided that they did contain amino acids 643-692: deletion of this part resulted in the disappearance of the reactivity. Testing of an extensive panel of the sera from HIV-1 seropositive or seronegative donors from Europe and Africa, including a selected group of donors before and after HIV-1 seroconversion, in a competition ELISA with horseradish peroxidase-conjugated K14, showed that the epitope recognized on gp41 is immunodominant and conserved. K14 does not neutralize HIV-1 infectivity or virus-mediated cell fusion, and does not mediate antibody-dependent cellular cytotoxicity.
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PMID:Production and characterization of a human monoclonal antibody, reactive with a conserved epitope on gp41 of human immunodeficiency virus type I. 169 24

Computer analyses of amino acid sequences in the human immunodeficiency virus-1 (HIV-1) envelope glycoprotein revealed that antigenic domains in the viral protein can be predicted on the basis of the physical properties of amino acids in the polypeptide chain. Relatively high values of surface probability, flexibility, and hydrophilicity were used as markers for domains of putative antigenicity. Comparison of the computer-predicted antigenic domains in the HIV-1 envelope with those reported experimentally indicate that computer analyses are able to predict antigenic domains. This study shows the usefulness of computer programs for the prediction of the antigenic domains in the HIV-1 envelope protein.
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PMID:Computer predictions of antigenic domains in human immunodeficiency virus-1 envelope glycoprotein: comparison with reported experimental data. 169 57


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