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

Using several HIV-1-specific antibodies and the immunogold labelling technique, we have detected and localized distinct viral proteins on ultrathin sections of HIV-1 infected cells embedded in the Lowicryl K4M resin. Monoclonal antibodies (MAbs) against p24, p17 and gp160/gp41 showed a preferential labelling on viral formations still attached to the cell membrane (budding process) or free in the extracellular space. The anti-p24 and the anti-p17 MAb yielded a gold labelling not only on mature but also on immature virions where the gold particles were associated with the ring-like electron-dense material. The three HIV-1-specific antibodies against p24, p17 and p55 yielded a cross-reaction with HIV-2 in agreement with the conservation of the internal antigenic determinants of both viruses. In all instances, there was no specific immunogold labelling over the cells, suggesting that once the virus structural proteins were synthesized, they were promptly utilized for virus assembly at the plasma membrane level.
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PMID:Localization by immunogold labelling of HIV-1 structural proteins on Lowicryl embedded HIV-1 infected cell ultrathin sections. 160 May 7

The binding of the human immunodeficiency virus envelope glycoprotein gp120 to the CD4 molecule is the initial step in the viral replicative cycle. This interaction is therefore an important target for therapeutic intervention for the treatment of human immunodeficiency virus infection. We designed an enzyme-linked immunosorbent assay which detects the interaction between recombinant soluble forms of CD4 and gp160. This assay could be used as an initial screen of libraries of synthetic chemical compounds and natural products.
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PMID:Simple assay to screen for inhibitors of interaction between the human immunodeficiency virus envelope glycoprotein and its cellular receptor, CD4. 160 91

The generation of memory B cells in response to vaccination with a baculovirus-derived recombinant gp160 candidate AIDS vaccine, VaxSyn HIV-1, was investigated in 12 healthy human volunteers who were immunized with VaxSyn HIV-1, hepatitis B vaccine, or alum adjuvant alone on days 1, 28, 180, and 540. Peripheral blood mononuclear cells were collected pre- and post-immunization and cultured unstimulated or with pokeweed mitogen (PWM), VaxSyn HIV-1 (rgp160), or HIV-1 lysate (iHIV-1) for 7 days before polyclonal and HIV-1-specific IgG production in culture supernatants (SNs) were measured. No differences were seen in the spontaneous or PWM-induced IgG production in SN from vaccinees and controls. Only vaccinee SN contained higher-than-normal levels of polyclonal IgG after stimulation with either rgp160 or iHIV-1, especially after the second and third booster immunizations on days 180 and 540, respectively. There were also contemporaneous increases in HIV-1-specific antibody in SN of all vaccinees, albeit at different time points throughout the study. We conclude that VaxSyn HIV-1 induces antigen-specific B-cell responses with the generation of memory B cells in vivo that can be reactivated in vitro to deliver an anamnestic response.
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PMID:B-cell activation and differentiation by HIV-1 antigens among volunteers vaccinated with VaxSyn HIV-1. 161 72

In this present report we compare the humoral immune response induced by immunization with an HIV-1 gp160 peptide corresponding to amino acid sequence 503-535 complexed with different adjuvants. Specifically, the antipeptide, anti-HIV-1 gp160 and neutralizing antibody responses were measured in groups of mice and baboons that received peptide 503-535 conjugated to a carrier protein in either saline, alum, or stearyl tyrosine. The highest antibody responses were induced when mice and baboons were immunized with peptide adsorbed on stearyl tyrosine. These data indicate that stearyl tyrosine represents a potent candidate as a nontoxic adjuvant not only for subunit viral vaccines, but also for HIV peptides.
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PMID:Adjuvanticity of stearyl tyrosine on the antibody response to peptide 503-535 from HIV gp160. 161 85

A total of 160 sera from HIV-1 infected individuals from Tanzania were examined for their fine specificity characteristics relative to 9 synthetic peptides that define HIV-1 gp160 epitopes. Immunorecessive and immunodominant epitopes were identified in both gp120 and gp41 based on serologic reactivity of these HIV-1 infected sera. A significant difference in fine specificity among HIV-1 infected individuals from Tanzania and the United States was observed for an immunodominant gp41 epitope. No significant differences in reactivity among asymptomatic vs. symptomatic HIV-1 infected individuals were detected for the selected HIV-1 gp160 epitopes defined by these peptides. The majority of sera from HIV-1 infected Tanzanians contained antibodies that recognized a peptide corresponding to the V3 region of gp120 from the HIV-1 MN isolate. These data suggest that regional isolates of HIV-1 may exist in Tanzania that differ from HIV-1 isolated in the United States. However, based on serology, HIV-1 isolates exhibiting sequences with HIV-1 MN V3 similarity may also be prevalent in Tanzania. The results of this study may be useful for the design of more effective AIDS diagnostic and therapeutic products for use worldwide.
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PMID:Fine specificity of the humoral immune response to HIV-1 GP160 in HIV-1 infected individuals from Tanzania. 161 99

The antiviral activity of 6-0-butanoylcastanospermine (MDL 28,574) [50% inhibitory concentration (IC50: 1.1 microM)] in JM cells infected with a recent isolate of HIV-1 (GB8), was compared with other inhibitors of glycoprotein-processing enzymes. N-butyldeoxynojirimycin (BuDNJ), deoxynojirimycin (DNJ), castanospermine (CAST) or the reverse transcriptase inhibitor 2'3'-dideoxycytidine (ddC) had activities of 56, 560, 29 and 0.1 microM, respectively. MDL 28,574 was at least 50 times more active than BuDNJ and less active but better tolerated in cell culture than ddC, two compounds currently undergoing clinical trials. The CAST derivative showed good protection in H9 cells infected with HIV-1 (RF; IIIB; U455), and HIV-2 (ROD), although the potency was less than that seen in the JM/GB8 system. HIV-1 glycoproteins, gp160 and gp120, synthesized in H9 cells chronically infected with HIV-1 (RF) and treated with MDL 28,574, were characterized by an increase in relative molecular weight of approximately 7-8000 kD. The ratio of gp120 to gp160 was markedly reduced in treated cells and provided further evidence that cleavage of the gp160 precursor molecule is a major consequence of the inhibition of glycoprotein processing. The intracellular target for MDL 28,574 was verified as alpha-glucosidase-I of the processing enzymes by the analysis of high-glucose glycopeptides recovered from treated mouse cells. This activity correlated with the antiviral effect observed against the growth of a mouse retrovirus, Moloney murine leukemia virus (MOLV), in mouse cells.
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PMID:6-0-butanoylcastanospermine (MDL 28,574) inhibits glycoprotein processing and the growth of HIVs. 165 79

Polyclonal B-cell activation is a characteristic feature of AIDS and of the AIDS-related complex. Since the immunoregulatory cytokine interleukin-6 (IL-6) plays a major role in inducing B-cell differentiation, we examined the effects of native human immunodeficiency virus type 1 envelope glycoproteins gp120 and gp160 on IL-6 induction. In this study, we have demonstrated that both gp120 and gp160 have the ability to induce IL-6 mRNA and biologically active IL-6 protein secretion in peripheral blood mononuclear cells in vitro. The envelope protein preparations had no detectable endotoxin as tested by the Limulus amebocyte lysate assay, and hence we can rule out the effect of contaminating endotoxin, which is a potent inducer of IL-6 in monocyte/macrophage cell cultures. In addition, we have shown that the envelope glycoproteins act directly on CD4(+)-cloned T cells to induce IL-6 production in the absence of monocytes. These findings indicate that monocytes and T cells both contribute to the secretion of IL-6, which plays an important role in the pathogenesis of B-cell activation in human immunodeficiency virus infection.
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PMID:Human immunodeficiency virus type 1 envelope glycoproteins gp120 and gp160 induce interleukin-6 production in CD4+ T-cell clones. 165 94

In a randomised phase I trial of a recombinant vaccina virus vaccine expressing the gp160 envelope gene of the human immunodeficiency virus (HIVAC-1e) 35 healthy, HIV-seronegative males, 31 of whom had a history of smallpox immunisation and 4 of whom were vaccinia naive, were vaccinated and then boosted 8 weeks later with HIVAC-1e or standard NY strain vaccinia virus. The frequency, duration, and titre of virus isolation from the vaccination site and occurrence of local side-effects were similar between the two groups of vaccinees. Vaccinia-naive (vac-n) subjects shed virus from the vaccination site for longer and at a higher titre than did vaccinia-primed (vac-p) individuals (19 vs 7 days and 10(7) vs 10(5) pfu/ml, respectively). In-vitro T-cell proliferative responses to one or more HIV antigen preparations developed in 13 of 16 vaccinia-primed subjects inoculated with HIVAC-1e. T-cell responses were, however, transient and in no subject did antibodies to HIV become detectable. The 2 vaccinia-naive subjects vaccinated with HIVAC-1e showed strong T-cell responses to homologous and heterologous strains of whole virus and to recombinant gp160 protein that remained detectable for over a year; antibodies to HIV envelope also developed in both. Recombinant vaccinia virus vaccines induce T-cell priming to the foreign gene products in most individuals. If used as the sole immunising agent they will be most efficacious in vaccinia-naive individuals.
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PMID:Safety of and immunological response to a recombinant vaccinia virus vaccine expressing HIV envelope glycoprotein. 167 28

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

In the present study inactivated human immunodeficiency virus type 1 (HIV-1) was conjugated to Brucella abortus and tested for immunogenicity in normal and anti-L3T4-treated BALB/c mice. HIV-BA was more immunogenic than uncoupled HIV in normal mice, since 6-fold less virus in HIV-BA preparations elicited higher titer responses than HIV-1 alone. Furthermore, the HIV-BA antibody response reached higher levels before the HIV-1 response. Immunoblot analysis showed that most of the HIV-1 antigens were recognized by antibodies induced by either HIV-1 or HIV-BA. Isotype analysis revealed that HIV-1 induced similar levels of IgG1 and IgG2a antibodies, whereas the IgG2a responses to HIV-BA were more pronounced than the IgG1 response. These different IgG subclass patterns suggest that conjugation of HIV-1 to BA changed the immunogenic nature of HIV-1. The requirement for helper T cells was examined by immunizing mice that were depleted of CD4+ T cells by in vivo anti-L3T4 treatment. Under these conditions the IgG responses to HIV-1 were completely eliminated. Although HIV-BA antibody responses were markedly reduced in anti-L3T4-treated mice, anti-HIV-1 antibodies, mainly of the IgG2a isotype, were produced. The antibodies generated by HIV-1 and HIV-BA immunization were also tested for their ability to inhibit syncytia formed by infecting CD4 + CEM cells with gp160 vaccinia. Sera from normal mice, immunized with either HIV-1 or HIV-BA were capable of inhibiting syncytia. In contrast, following anti-L3T4 treatment, only mice immunized with HIV-BA, but not HIV-1, produced antibodies capable of inhibiting syncytia.
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PMID:Production of a novel antigen by conjugation of HIV-1 to Brucella abortus: studies of immunogenicity, isotype analysis, T-cell dependency, and syncytia inhibition. 167 17


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