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

A successful AIDS vaccine must elicit an immune state that will prevent the establishment of an HIV-1 persistent infection. This is a unique and difficult goal for a vaccine. Most vaccines elicit or prime for immune responses that prevent or attenuate the expression of clinical disease following infection with the pathogen. However, current evidence suggest that, following persistent infection with HIV-1, antiviral immune responses do not prevent the long-term progression to disease. Hence, it seems that the development of the persistent infection must be prevented. The ability of the immune response to accomplish this goal depends upon the efficiency with which the virus establishes persistence in the host. This is unknown for HIV-1. As a result, early efforts at vaccine development have focused on humoral immune responses directed against the virus particle in the attempt to prevent any infection of the host's cells. Studies with chimpanzees, as a model for HIV-1 infection, suggest that virus-neutralizing antibodies directed against the third hypervariable (V3) domain of the viral gp120 envelope glycoprotein may be particularly effective in preventing this infection. Studies also are in progress, both in chimpanzees and humans, to define the immunogenicity and effectiveness of various immunogens derived from the viral envelope and core structural proteins. Efforts that have concentrated on the gp120 V3 domain (or PND) have defined the extent of this region's variability and have established elements of generally conserved structure and sequence. The construction of these elements into practical and effective immunogens is an important goal. Finally, it is essential that basic studies be performed to determine if humoral or cellular immune responses directed against virus-infected cells would aid in preventing the establishment of an HIV-1 persistent infection. Such immune responses, if effective and in conjunction with specific virus-neutralizing antibody responses, would enhance the probability that an effective HIV-1 vaccine could be developed.
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PMID:Human immunodeficiency virus. 160 Mar 83

The observation that approximately 70% of HIV-infected pregnant women do not transmit infection vertically suggests that antibody therapy may be effective in the prevention of transmission of HIV infection from mother to child. Currently, there is an incomplete understanding of the processes involved in vertical transmission of HIV infection. The elucidation of the serological basis of maternal immunity as it relates to protection from vertical transmission is the goal of this study. We have screened 20 maternal sera from HIV+ individuals of known vertical transmission status for reactivity with 31 peptides spanning the entire envelope glycoprotein of HIV-1. Of interest was reactivity to regions outside of the V3 loop of gp120. The findings have been examined in relationship to transmission status, as well as to in vitro anti-HIV-1 biological activity. Our results indicate that lack of vertical transmission is correlated with high viral neutralization activity, but not with antisyncytial activity nor with binding to the V3 peptides examined in this study. Also, the transmission group bound to fewer gp41 peptides when compared with the nontransmission group, suggesting that immune responses to gp41 may be important in preventing transmission. These findings may provide insights into the design of passive immunotherapies.
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PMID:Vertical transmission of human immunodeficiency virus (HIV) infection. Reactivity of maternal sera with glycoprotein 120 and 41 peptides from HIV type 1. 160 99

To study the intracellular transport and biological properties of the human immunodeficiency virus type 1 (HIV-1) transmembrane glycoprotein (TM; gp41), we constructed a truncated envelope gene in which the majority of the coding sequences for the surface glycoprotein (SU; gp120) were deleted. Transient expression of this truncated env gene in primate cells resulted in the biosynthesis of two proteins with M(r)s of 52,000 and 41,000, respectively. Immunofluorescence studies with antibodies to the HIV-1 TM protein indicated that the intracellular and surface localization of these proteins were indistinguishable from those of the native HIV-1 gp120-gp41 complex. These results indicate that the oligosaccharide processing and cell surface transport of the HIV-1 TM protein were not dependent on the presence of the receptor binding subunit, gp120. Syncytium formation was readily detected upon expression of the deleted HIV-1 env gene into COS and CD4+ HeLa cell lines, suggesting that in the absence of gp120, the TM protein retained biological activity. This observation was confirmed by infection of primate and mouse cell lines with a recombinant vaccinia virus (vvgp41) expressing the truncated HIV-1 env gene. These results strongly suggest that (i) the two biological activities of the HIV-1 envelope glycoprotein can occur independently and (ii) the association of the two glycoprotein subunits may restrict the fusion activity of the transmembrane component to CD4+ cells.
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PMID:The transmembrane glycoprotein of human immunodeficiency virus type 1 induces syncytium formation in the absence of the receptor binding glycoprotein. 160 36

Vaccines prepared from the envelope glycoprotein, gp120, of the common laboratory isolate of human immunodeficiency virus type 1 (HIV-1) (IIIB/LAV-1) elicit antibodies that neutralize the homologous virus but show little if any cross-neutralizing activity. This may be because the principal neutralizing determinant (PND) of gp120 is highly unusual in the IIIB/LAV-1 strain and is not representative of those found in the majority of field isolates. We have now examined the immunogenicity of recombinant gp120 prepared from the MN strain of HIV-1 (MN-rgp120), whose PND is thought to be representative of approximately 60% of the isolates in North America. Our results show that MN-rgp120 is a potent immunogen and elicits anti-gp120 titers comparable to those found in HIV-1-infected individuals. While both MN-rgp120 and IIIB-rgp120 induced antibodies able to block gp120 binding to CD4, strain-specific and type-common blocking antibodies were detected. Finally, antibodies to MN-rgp120 but not to IIIB-rgp120 were effective in neutralizing a broad range of laboratory and clinical isolates of HIV-1. These studies demonstrate that susceptibility or resistance to neutralization by antibodies to gp120 correlates with the PND sequence and suggest that the problem of antigenic variation may not be insurmountable in the development of an effective AIDS vaccine.
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PMID:Neutralization of multiple laboratory and clinical isolates of human immunodeficiency virus type 1 (HIV-1) by antisera raised against gp120 from the MN isolate of HIV-1. 160 54

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

Replication competent chimeric viruses that express the gag and pol proteins of SIVmac and the env proteins of HIV-1 were made. One such chimeric virus, SHIV-4, that expresses the vif, vpx, vpr, and nef regulatory genes of SIV and the tat and rev regulatory genes of HIV-1 replicated efficiently in cynomolgus monkeys. This model system can be used to evaluate the efficacy of anti-HIV-1 vaccines directed at the envelope glycoproteins, anti-HIV-1 envelope glycoprotein antiserum or monoclonal antibodies, and anti-HIV-1 drugs designed to inhibit the tat, rev, or env functions.
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PMID:Infection of cynomolgus monkeys with a chimeric HIV-1/SIVmac virus that expresses the HIV-1 envelope glycoproteins. 161 62

Here, Lee Eiden and Jeffrey Lifson present a model for HIV envelope glycoprotein-CD4 interactions that attempts to reconcile recent, seemingly conflicting, structural, biochemical and biological observations. Central to this model is the involvement of both the CDR2-like and CDR3-like domains of CD4 in the interaction with gp120, leading to a conformational change and dissociation of gp120 from the gp120-gp41 complex.
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PMID:HIV interactions with CD4: a continuum of conformations and consequences. 162 47

Human T cell lines specific for different peptides of HIV envelope glycoprotein gp120 have been used as probes to identify the availability of functional MHC-peptide complexes on APC. MHC-peptide complexes recognized by T cells specific for peptide 24 (amino acids 225-240) are no longer available on the surface of APC after interaction with irradiated (binding nonproliferating) T cells with the same fine specificity. On the contrary, MHC-peptide complexes recognized by T cells specific for peptide 30 (amino acids 285-300) were functionally available and could stimulate T cells with such a specificity. The reciprocal experiment yielded similar results. The same data were also reproduced with another pair of gp120 peptides. These data demonstrate that upon clustering of peptide-specific T cells with presenting cells presentation of the same peptide to a second cohort of T cells with identical specificity is abolished, suggesting that a selective functional depletion of the MHC-peptide complexes engaged with specific T cells occurs at the surface of the presenting cells. The depletion does not affect other MHC molecules complexed with unrelated peptides.
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PMID:Selective functional depletion of HIV gp120 peptides complexed with MHC from antigen-presenting cells engaged with specific T lymphocytes. 163 69

Visna virus, a lentivirus of sheep, causes fusion of susceptible cells. Fusion has previously been shown to be mediated by the viral envelope glycoprotein. The transmembrane protein of visna virus contains a hydrophobic region at its amino terminus. This region is similar to the fusion epitopes of the orthomyxoviruses and paramyxoviruses. This region is located in a position similar to that of the fusion epitopes in the transmembrane proteins of HIV-1 and SIV. To determine the role of this hydrophobic region in visna virus-induced cell fusion, a peptide of 24 amino acids corresponding to this region was synthesized. The peptide alone induces fusion of goat cells. Antibodies to this peptide inhibit both viral-induced cell fusion and peptide fusion in goat cells. Further, the direct fusion of cells by this peptide is a unique observation and may be useful for studying the fusion epitopes of other lentiviruses. Thus, this hydrophobic region appears to be one epitope responsible for visna virus-induced cell fusion.
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PMID:Identification of the fusion domain in the visna virus transmembrane protein. 165 2

The central nervous system manifestations of AIDS were originally thought to consist solely of white matter lesions, but recent evidence has shown that a substantial degree of neuronal loss can also occur. This review presents evidence for HIV-related toxic factors that may account at least in part for this newly-recognized neuronal injury. One potential neurotoxin is the HIV-1 envelope glycoprotein gp-120 or a fragment of this molecule. This coat protein is shed by the virus and potentially released from HIV-infected immune cells. In tissue culture experiments on rodent neurons, gp120 produces an early rise in intracellular calcium concentration and, subsequently, delayed-onset neurotoxicity. In addition, HIV-infected macrophages or microglia release as yet undefined toxic factor(s) that kill rodent, chick, and human neurons in vitro. It is as yet unknown if one of these macrophage toxic factors might represent a gp120 fragment, or alternatively, if gp120, in the absence of HIV-1 infection, might be capable of activating macrophages to release these toxic factor(s). In at least some neuronal cell types, gp120-induced neurotoxicity can be prevented by antagonists of L-type voltage-dependent calcium channels or by antagonists of N-methyl-D-aspartate (NMDA, a subtype of glutamate receptor). Degradation of endogenous glutamate also protects neurons from gp120-related neuronal injury, suggesting that gp120 and glutamate are both necessary for neuronal cell death as synergistic effectors. Antagonists acting at the other types of glutamate receptors (non-NMDA antagonists) are ineffective in affording protection from gp120.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:HIV-related neurotoxicity. 166 8


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