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

Genetic comparison of SIVmac to the human retroviruses generally associated with AIDS revealed a closer relationship to HIV-2 than to HIV-1. A common feature differentiating SIV and HIV-2 from HIV-1 is the size of the transmembrane portion of the envelope, which is smaller (gp32) in SIVmac and HIV-2 than in HIV-1 (gp41). The presence of this truncated form of the transmembrane glycoprotein in SIVmac and HIV-2 virions is apparently related to the presence of a translation termination codon in the env gene of all SIV proviruses analyzed as well as in one HIV-2 provirus. Since the carboxy terminus of the envelope transmembrane protein has been implicated in the cytopathic effect of HIV-1 in vitro, we decided to investigate whether putative expression of the open reading frame located after the termination codon correlates with the pathogenicity of SIVmac in vivo. We generated two synthetic peptides from the inferred amino acid sequence of SIVmac and tested their reactivity by Western blot against the sera of naturally and experimentally infected monkeys as well as against sera of HIV-2-infected individuals. Our results indicate that the protein synthesized from this open reading frame is expressed in vivo, since an immunoresponse can be detected against the synthetic peptides in two of three experimentally SIVmac-infected animals. However, no correlation can be found between its expression and disease progression at this time. Furthermore, a rabbit immune serum raised against the synthetic peptide failed to identify any specific protein in SIVmac-infected cells.
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PMID:The simian immunodeficiency virus envelope open reading frame located after the termination codon is expressed in vivo in infected animals. 314 95

Using synthetic peptides, we characterized the B-lymphocyte (antibody) and T-lymphocyte (proliferation) responses to an immunodominant epitope of human immunodeficiency virus type 1 (HIV-1) located near the amino-terminal end of the transmembrane glycoprotein (env amino acids 598 to 609). Both immunoglobulin M (IgM) and IgG antibodies against this epitope appeared early after primary infection with HIV-1. In an animal model, the IgG response to a synthetic peptide derived from this sequence was T-helper-cell dependent, whereas the IgM response was T-cell independent. In addition, antibody generated by immunization with this peptide had HIV-1-neutralizing activity. Greater than 99% (201 of 203) of patients infected with HIV-1 generated antibody to this peptide in vivo; however, only 24% (7 of 29) had T cells that proliferated in response to this peptide in vitro. These observations suggest that different HIV-1 gp41 epitopes elicit B-cell and T-cell immune responses.
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PMID:B- and T-lymphocyte responses to an immunodominant epitope of human immunodeficiency virus. 326 Jun 30

gp41, the transmembrane glycoprotein of HIV-1, has been shown to be non-covalently associated with gp120. We have shown that it also binds human C1q. To analyze the interaction site(s) of gp41 with these two molecules, we established an enzyme-linked immunosorbent assay (ELISA) system using recombinant soluble gp41 [amino acids (aa) 539-684] and peptides thereof. In the cell-external part of gp41 three sites (aa 526-538, aa 590-613 and aa 625-655) were found to bind both gp120 and C1q. That gp120 and C1q use the same sites was evidenced by the fact that these proteins competed with each other for the same sites in recombinant soluble gp41 and gp41 peptides. It could be demonstrated by ELISA, that rabbit antibodies against human C1q recognized gp120, and rabbit antibodies against gp120 cross-reacted with C1q. Rabbit anti-gp120, HIV-1-positive human sera and anti-gp120 obtained from such sera agglutinated sensitized sheep erythrocytes with human C1q (EAC1q). These data suggest that in addition to functional homology between C1q and gp120 structural homology between these two molecules exists. This molecular mimicry might become the basis for immunologically relevant autoimmune phenomena.
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PMID:The envelope glycoprotein of HIV-1 gp120 and human complement protein C1q bind to the same peptides derived from three different regions of gp41, the transmembrane glycoprotein of HIV-1, and share antigenic homology. 750 42

B lymphocytes from tonsillar tissue of an asymptomatic HIV-1-seropositive subject were transformed with Epstein-Barr virus (EBV) and tested for the production of HIV-1-specific antibodies by ELISA, using purified HIV-1SF2.2F11, a monoclonal antibody derived from a transformed line, is of the IgG1 subclass and recognizes an epitope in the conserved region of the envelope transmembrane glycoprotein gp41, which is expressed on the surface of HIV-infected T cells. The antibody does not mediate the lysis of infected T cells in antibody-dependent cellular cytotoxicity (ADCC) assays and does not neutralize the infectivity of HIV-1SF2 or the homologous isolate HIV-1TT2.2F11 appears to be the first anti-gp41 human monoclonal antibody that enhances the infectivity of an HIV-1 strain (i.e., SF128A) in the absence of complement.
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PMID:An anti-gp41 human monoclonal antibody that enhances HIV-1 infection in the absence of complement. 751 15

We have used cells infected with the HIV-1 molecular clone HX10 to study the binding of monoclonal antibodies (mAbs) to different epitopes within the extracellular domain of the HIV-1 transmembrane glycoprotein gp41. Gp41 mAb binding to the infected cells at 4 degrees was variable but weaker than the binding of an anti-gp120/V3 loop mAb and increased substantially for three of the gp41 antibodies at 37 degrees. Treatment of the cells with soluble CD4 (sCD4) at 37 degrees increased gp41 mAb binding to epitopes spanning residues 521-663, implying that these regions had probably been masked by gp120, which following interaction with sCD4 had subsequently dissociated from gp41. By contrast, the binding of a mAb to residues 662-667 which form a neutralization epitope was reduced by sCD4 binding. Another region which has been described as containing a neutralization epitope spans residues 725-750. MAbs to this region bound equally well to noninfected and HIV-infected cells, and binding was not increased in the presence of sCD4. These data strongly imply that this epitope is not exposed on the external surface of the membrane, a finding in accord with the proposed cytoplasmic localization of this region.
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PMID:Epitope exposure on functional, oligomeric HIV-1 gp41 molecules. 753 Apr

Recent experimental evidence has shown that the C-terminal peptide of the HIV/SIV transmembrane glycoprotein 41 (gp41) can bind very tightly to calmodulin (CaM). These findings imply a potential mechanism for HIV/SIV cytopathogenesis, which involves the uncoupling of some critical cellular signal transduction pathways that are normally mediated by CaM. Here, we present circular dichroism (CD) and nuclear magnetic resonance (NMR) spectroscopy studies of a 28-residue synthetic peptide, SIV-L, corresponding to the C-terminal portion of the SIV transmembrane glycoprotein gp41. CD studies recorded in aqueous solution show a dramatic increase in the amount of alpha-helical structure of the SIV-L peptide upon binding to calcium-CaM. Two-dimensional NMR experiments were performed to determine the secondary structure of the peptide in 25% aqueous trifluoroethanol solution. In this alpha-helix inducing solvent, the observed nuclear Overhauser effects, as well as the alpha 1H and alpha 13C chemical shift changes, demonstrate that a continuous alpha-helix is formed from W3 to L28, although there is some distortion around P17. This result is in accordance with those obtained for many other CaM-binding peptides. Subsequent one-dimensional NMR titration experiments of calcium-CaM and the SIV-L peptide suggest that the peptide can bind to CaM with a 1:1 stoichiometry and that the peptide binding involves both the N- and C-lobe of CaM. However, gel mobility shift assays suggest that the peptide CaM interaction may be more complicated, as oligomeric forms of CaM and the SIV-L peptide were found. These studies provide a potential molecular basis for HIV/SIV cytopathogenesis.
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PMID:Characterization of the calmodulin binding domain of SIV transmembrane glycoprotein by NMR and CD spectroscopy. 765 23

The surface of HIV-1, like that of other retroviruses, is studied with virally encoded glycoproteins which appear ultrastructurally as electron-dense spikes or knobs. The glycoprotein that forms the spike structure, gp120, is non-covalently bound to the transmembrane glycoprotein gp41. Mature HIV-1 virions do not have as many spikes as the genetically related retroviruses HIV-2 and SIV. gp120 is lost from HIV-1 during viral morphogenesis and after incubation of the virus with the soluble form of cellular receptor CD4. In this study we used ultrastructural cytochemistry and morphometry to quantitate the distribution of envelope glycoprotein spikes on budding and mature HIV-1 virions and to look for alternatives to the laborious and somewhat subjective spike-counting technique for envelope spike analysis on HIV-1. HIV-1, strain HTLV-IIIB, was examined after staining of envelope glycoproteins with either tannic acid, immunogold staining for gp120 (gp120-immunogold), or lectin-gold staining with concanavalin A for mannose residues (ConA-HRP-gold) and frequency distributions of spikes or gold particles per micron HIV-1 membrane generated. Envelope spikes were normally distributed on membranes of budding and mature HIV-1. However, the density of spikes per micron viral membrane on mature HIV-1 virions was approximately 50% of that observed on budding virions. ConA-HRP-gold and gp120-immunogold did not efficiently label budding virions. The shape of the frequency distribution for ConA-HRP-gold particles on mature virions was similar to that for envelope spikes and could be used to quantitate envelope glycoproteins on HIV-1. In addition, ConA-HRP-gold staining was able to detect the loss of envelope proteins after treatment of virus with soluble CD4. gp120-immunogold labeling was patchy and many virions were unlabeled. ConA-HRP-gold staining proved to be a rapid, reliable, and easily quantifiable method for estimation of envelope glycoprotein density on mature HIV-1. However, the loss of spike structures throughout the life cycle of HIV-1 can effectively be determined only by direct spike counting.
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PMID:Morphometric analysis of envelope glycoprotein gp120 distribution on HIV-1 virions. 767 71

In order to develop a reliable and inexpensive serodiagnostic method, part of the transmembrane glycoprotein gene of HIV-1, gp41', (HIV-env 548-646) was cloned into an expression vector, pCT10 with a sequence encoding a hydroxylamine cleavage site and with a part of Lac Z gene (Lac 2": 834 base pairs) as a fusion partner. Overexpression of Lac Z"-gp41' was induced in E. coli and the gp41' fusion protein was purified to homogeneity by centrifugation, hydroxylamine cleavage and an ion-exchange chromatography. Western blot analysis and enzyme-linked immunosorbant assay (ELISA) using the purified gp41 fragment showed high sensitivity and specificity of gp41 as an antigen to detect anti HIV-1 antibodies in testing human sera. These results suggest that this simple and rapid purification method is reliable for obtaining a large quantity of purified gp41'.
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PMID:Rapid and simple purification of human immunodeficiency virus 1 epitope gp41. 767 96

We have investigated the molecular basis of biological differences observed among cell line-adapted isolates of the human immunodeficiency virus types 1 and 2 (HIV-1 and HIV-2) and the simian immunodeficiency virus (SIV) in response to receptor binding by using a soluble form of CD4 (sCD4) as a receptor mimic. We find that sCD4 binds to the envelope glycoproteins of all of the HIV-1 isolates tested with affinities within a threefold range, whereas those of the HIV-2 and SIV isolates have relative affinities for sCD4 two- to eightfold lower than those of HIV-1. Treatment of infected cells with sCD4 induced the dissociation of gp120 from gp41 and increased the exposure of a cryptic gp41 epitope on all of the HIV-1 isolates. By contrast, neither dissociation of the outer envelope glycoprotein nor increased exposure of the transmembrane glycoprotein was observed when sCD4 bound to HIV-2- or SIV-infected cells. Moreover, immunoprecipitation with sCD4 resulted in the coprecipitation of the surface and transmembrane glycoproteins from virions of the HIV-2 and SIV isolates, whereas the surface envelope glycoprotein alone was precipitated from HIV-1. However, treatment of HIV-1-, HIV-2-, and SIV-infected cells with sCD4 did result in an increase in exposure of their V2 and V3 loops, as detected by enhanced antibody reactivity. This demonstrates that receptor binding to the outer envelope glycoprotein induces certain conformational changes which are common to all of these viruses and others which are restricted to cell line-passaged isolates of HIV-1.
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PMID:Conformational changes induced in the envelope glycoproteins of the human and simian immunodeficiency viruses by soluble receptor binding. 769 70

The matrix (MA) protein of human immunodeficiency virus type 1 (HIV-1) forms the outer protein shell directly underneath the lipid envelope of the virion. The MA protein has a key role in different aspects of virus assembly, including the incorporation of the HIV-1 Env protein complex, which contains a transmembrane glycoprotein with an unusually long cytoplasmic tail. In this study, we compared the abilities of HIV-1 MA mutants to incorporate Env protein complexes with long and short cytoplasmic tails. While the mutant particles failed to incorporate the authentic HIV-1 Env protein complex, they retained the ability to efficiently and functionally incorporate the amphotropic murine leukemia virus Env protein complex, which has a short cytoplasmic tail. Moreover, incorporation of the autologous Env protein complex could be restored by a second-site mutation that resulted in the truncation of the cytoplasmic tail of the HIV-1 transmembrane glycoprotein. Remarkably, the second-site mutation also restored the ability of MA mutants to replicate in MT-4 cells. These results imply that the long cytoplasmic tail of the transmembrane glycoprotein is responsible for the exclusion of the HIV-1 Env protein complex from MA mutant particles.
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PMID:Rescue of human immunodeficiency virus type 1 matrix protein mutants by envelope glycoproteins with short cytoplasmic domains. 774 30


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