Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0021051 (immunodeficiency)
 71,517 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Carbohydrate structures are often involved in the initial adhesion of pathogens to target cells. In the present study, a panel of anticarbohydrate monoclonal antibodies (MAbs) was tested for their ability to inhibit in vitro human immunodeficiency virus infectivity. MAbs against three different N- and O-linked carbohydrate epitopes (LeY, A1, and sialyl-Tn) were able to block infection by cell-free virus as well as inhibit syncytium formation. Inhibition of virus infectivity was independent of virus strain (HTLVIIIB or patient isolate SSI-002), the cell line used for virus propagation (H9 or MT4), and the cell type used as the infection target (MT4, PMC, or selected T4 lymphocytes). Inhibition was observed when viruses were preincubated with MAbs but not when cells were preincubated with MAbs before inoculation, and the MAbs were shown to precipitate 125I-labeled gp120. The MAbs therefore define carbohydrate structures expressed by the viral envelope glycoprotein gp120, indicating that glycans of the viral envelope are possible targets for immunotherapy or vaccine development or both.
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PMID:Inhibition of human immunodeficiency virus (HIV) infection in vitro by anticarbohydrate monoclonal antibodies: peripheral glycosylation of HIV envelope glycoprotein gp120 may be a target for virus neutralization. 169 49

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

Among 102 brains obtained from patients with acquired immune deficiency syndrome (AIDS), 34 cases with subacute AIDS encephalitis were characterized by immunohistochemistry using an antibody that binds to a human immunodeficiency virus-1 (HIV-1) envelope glycoprotein, gp41. This glycoprotein was detected in mononucleated and/or multinucleated cells in 90% of adult and 50% of pediatric brains with subacute AIDS encephalitis. In addition, many gp41-positive cells with bipolar or multipolar processes were found in 10 cases, and these cells occurred most frequently in the basal ganglia and internal capsule. The phenotype of the gp41-positive cells was determined using an improved double-labeling immunohistochemical technique that employed beta-galactosidase and peroxidase conjugated reagents. Cell-type specific markers for double-labeling included: Ricinus communis agglutinin-1 (RCA-1) for macrophages and microglia; Ulex europaeus agglutinin-1 for endothelium; anti-glial fibrillary acidic protein (GFAP) for astrocytes; anti-amyloid precursor protein for neurons; and anti-leukocyte common antigen for leukocytes. Results of double-immunostaining revealed that gp41-positive cells of all morphologic types, including cells with bipolar or multipolar processes, were double-labeled with RCA-1, but not with markers for astrocytes, neurons, or endothelia. These findings support the contention that HIV-1 infection of the CNS is predominantly restricted to cells of the macrophage/microglia lineage.
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PMID:Cellular localization of an HIV-1 antigen in subacute AIDS encephalitis using an improved double-labeling immunohistochemical method. 169 70

Inhibition of infectivity, cytopathicity, and binding by soluble CD4 was determined for several human immunodeficiency virus (HIV)-1 and HIV-2 strains. Although infectivity and binding of both groups were blocked equally well by OKT4A, HIV-2 viruses were more refractory to inhibition by soluble CD4. Rates of envelope shedding, as determined by thermal stability, did not differ between HIV-1 and HIV-2; however, Scatchard plot analysis of radiolabeled virus binding revealed that fewer HIV-2 virions were bound to CD4+ cells under saturating conditions. The HIV-2 viruses also possessed consistently greater infectivity, whereas greater concentrations of gp120 were found in supernatants of HIV-1-infected cells and in HIV-2 virus pellets, suggesting that more envelope glycoprotein remains associated with HIV-2 virions. This factor may contribute to the observed in-vitro resistance of HIV-2 viruses to soluble CD4.
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PMID:Differences in the interaction of HIV-1 and HIV-2 with CD4. 169 76

The phenomenon of interference was exploited to isolate low-abundance noncytopathic human immunodeficiency virus type 1 (HIV-1) variants from a primary HIV-1 isolate from an asymptomatic HIV-1-seropositive hemophiliac. Successive rounds of virus infection of a cytolysis-susceptible CD4+ cell line and isolation of surviving cells resulted in selective amplification of an HIV-1 variant reduced in the ability to induce cytolysis. The presence of a PvuII polymorphism facilitated subsequent amplification and cloning of cytopathic and noncytopathic HIV-1 variants from the primary isolate. Cloned virus stocks from cytopathic and noncytopathic variants exhibited similar replication kinetics, infectivity, and syncytium induction in susceptible host cells. The noncytopathic HIV-1 variant was unable, however, to induce single-cell killing in susceptible host cells. Construction of viral hybrids in which regions of cytopathic and noncytopathic variants were exchanged indicated that determinants for the noncytopathic phenotype map to the envelope glycoprotein. Sequence analysis of the envelope coding regions indicated the absence of two highly conserved N-linked glycosylation sites in the noncytopathic HIV-1 variant, which accompanied differences in processing of precursor gp160 envelope glycoprotein. These results demonstrate that determinants for syncytium-independent single-cell killing are located within the envelope glycoprotein and suggest that single-cell killing is profoundly influenced by alterations in envelope sequence which affect posttranslational processing of HIV-1 envelope glycoprotein within the infected cell.
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PMID:Cloning and characterization of human immunodeficiency virus type 1 variants diminished in the ability to induce syncytium-independent cytolysis. 169 54

Fresh peripheral blood mononuclear cells from human immunodeficiency virus-1 (HIV-1) seropositive donors can lyse target cells expressing the envelope glycoprotein in vitro. In most cases, this antigen-specific lysis is not mediated by T lymphocytes. Lymphoblastoid cell lines infected with recombinant vaccinia viruses expressing different forms of the envelope protein of HIV-1 were used as target cells in chromium-release assays of primary cytotoxic effector cells and of antibody-dependent cellular cytotoxicity (ADCC). By depleting effector cells of CD16+ lymphocytes, or by blocking target cell lysis with an anti-human IgG serum, primary env-specific lysis was found to be due to ADCC, the effector cells being armed in vivo with specific, cytophilic antibodies. This phenomenon is dependent on cell surface expression of the envelope protein and is directed against both gp120 and gp41. Human HIV-1 antibody-positive sera are able to mediate ADCC against HIV-infected CD4+ T lymphocytes, suggesting a possible role of ADCC in the natural infection.
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PMID:Primary cytotoxicity against the envelope glycoprotein of human immunodeficiency virus-1: evidence for antibody-dependent cellular cytotoxicity in vivo. 169 5

Human immunodeficiency virus (HIV) binds to cells via an interaction between CD4 and the virus envelope glycoprotein, gp120. Previous studies have localized the high affinity binding site for gp120 to the first domain of CD4, and monoclonal antibodies (mAbs) reactive with this region compete with gp120 binding and thereby block virus infectivity and syncytium formation. Despite a detailed understanding of the binding of gp120 to CD4, little is known of subsequent events leading to membrane fusion and virus entry. We describe two new mAbs reactive with the third domain of CD4 that inhibit steps subsequent to virus binding critical for HIV infectivity and cell fusion. Binding of recombinant gp120 or virus to CD4 is not inhibited by these antibodies, whereas infection and syncytium formation by a number of HIV isolates are blocked. These findings demonstrate that in addition to virus binding, CD4 may have an active role in membrane fusion.
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PMID:Novel anti-CD4 monoclonal antibodies separate human immunodeficiency virus infection and fusion of CD4+ cells from virus binding. 169 11

We have previously described a recombinant protein, designated CD4(178)-PE40, consisting of the human immunodeficiency virus (HIV) envelope glycoprotein-binding region of human CD4 linked to the translocation and ADP-ribosylation domains of Pseudomonas aeruginosa exotoxin A. By virtue of its affinity for gp120 (the external subunit of the HIV envelope glycoprotein), the hybrid toxin selectively binds to and kills HIV-1-infected human T cells expressing surface envelope glycoprotein and also inhibits HIV-1 spread in mixed cultures of infected and uninfected cells. We now report that CD4(178)-PE40 and reverse transcriptase inhibitors exert highly synergistic effects against HIV-1 spread in cultured human primary T cells. Furthermore, combination treatment can completely eliminate infectious HIV-1 from cultures of human T-cell lines. This conclusion is based on protection of a susceptible cell population from HIV-induced killing, complete inhibition of virus protein accumulation, and elimination of HIV DNA (as judged by quantitative polymerase chain reaction analysis). The results highlight the therapeutic potential of treatment regimens involving combination of a virostatic drug that inhibits virus replication plus an agent that selectively kills HIV-infected cells.
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PMID:Elimination of infectious human immunodeficiency virus from human T-cell cultures by synergistic action of CD4-Pseudomonas exotoxin and reverse transcriptase inhibitors. 170 Oct 55

The cytopathic effects of human immunodeficiency virus type 1 (HIV-1) infection are specific for cells that express the CD4 viral receptor and consist of syncytium formation and single-cell lysis. Here we report that a mutation (517A) affecting the amino terminus of the HIV-1 gp41 transmembrane envelope glycoprotein resulted in a virus that was markedly less cytopathic than was wild-type HIV-1. In systems in which cell-to-cell transmission of HIV-1 occurred, the replication ability of the 517A virus was comparable with that of the wild-type virus. Even though the levels of viral protein expression, virion production, and interaction of the envelope glycoproteins with CD4 were similar for the 517A and wild-type viruses, both syncytium formation and single-cell lysis were attenuated for the 517A mutant virus. These results demonstrate that an envelope glycoprotein region important for mediating post-receptor binding events in cell membrane fusion is important for the induction of cytopathic effects by HIV-1. These results also indicate that levels of HIV-1 viral proteins or viral particles produced in infected cells are in themselves not sufficient to induce cytopathic effects.
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PMID:Attenuation of human immunodeficiency virus type 1 cytopathic effect by a mutation affecting the transmembrane envelope glycoprotein. 170 59


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