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

The cytopathic effects of HIV-1 produced by direct infection of human T cells do not account for the disproportionate loss of CD4-positive lymphocytes during the course of HIV infection. Previous studies have demonstrated the inhibition of uninfected human T cell activation and proliferation by the HIV-1 envelope glycoproteins, presumably due to gp120-CD4 interactions. To examine the ability of HIV-1 to inhibit T cell proliferation in the absence of both direct infection and gp120-CD4 interactions, we tested the effect of HIV-1 on mouse T cell proliferation. Culture media containing HIV-1 released from infected cells inhibited T lymphocyte proliferation in response to interleukin-2 (IL-2). Studies to explore the mechanism of this inhibition suggested that the decrease in proliferation resulted from interactions between HIV-1 and the mouse cells, but did not involve IL-2/IL-2 receptor interactions. We used monoclonal antibodies to demonstrate that the HIV-1 envelope glycoproteins were required for the inhibition of murine T cell proliferation. Anti-gp120 antibodies completely restored proliferation, indicating that the surface protein gp120 was primarily required for the inhibition of proliferation. However, antibodies directed against the transmembrane protein of HIV-1 (gp41) also partially restored lymphocyte proliferation. The functional significance of the HIV-1 envelope protein epitopes recognized by the monoclonal antibodies is discussed.
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PMID:CD4-independent inhibition of lymphocyte proliferation mediated by HIV-1 envelope glycoproteins. 128 Mar 85

To allow the precise definition of the anti-lentiviral immune response in the natural host and to facilitate the development of an alternative animal model for vaccine development, we are identifying the immunogenic domains of SIVagm proteins. First, a total of 173 synthetic 15-mer peptides with an overlap of 10 amino acids were produced spanning the entire envelope glycoprotein of the molecular clone SIVagm3. These peptides were used as antigen in enzyme-linked immunosorbent assays for identifying regions recognized by antibodies from naturally infected African green monkeys and monkeys infected with a molecular clone. Regions corresponding to the HIV-1 V3, the transmembrane protein (TMP) "Gnann peptide", and the C-terminal area of the outer envelope protein were shown to be immunodominant. These regions were re-synthesized as 15-mer peptides with an overlap of 14 amino acids and used to precisely map the epitopes recognized. Sera from 93 captive and 61 wild animals were tested by SIVagm-specific Western blot (WB) and for ELISA reactivity against the immunodominant TMP peptide. One hundred percent (76/76) of the WB-positive captive animals and 98% (41/42) wild WB-positive animals also reacted against the peptide. In contrast, only 62% of the WB-positive sera reacted with the "V3" epitope and 46% with the gp130 C-terminal epitope.
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PMID:B-cell epitope mapping of the entire SIVagm envelope glycoprotein including fine mapping of immunogenic regions. 137 90

Monoclonal antibodies (MAbs) were raised against the transmembrane protein (TM) gp41 of human immunodeficiency virus type 1 (HIV-1, strain HTLV-IIIB). The reactivity of three TM-specific MAbs was investigated in several tests, ELISA, immunostaining of Western blots, immunofluorescence and an alkaline phosphatase-anti-alkaline phosphatase assay. Epitope mapping was done by using overlapping gp41 peptides produced as Escherichia coli fusion proteins and synthetic peptides. In an in vitro assay, all three MAbs showed enhancing effects on HIV-1 infection after single or repeated treatment with the purified MAbs at concentrations of 6 to 25 micrograms/ml. The enhancing domain is located between amino acids 724 and 752 of the env protein sequence. Homologous peptides based on this sequence were used for analysis of sera from 100 individuals at different stages of HIV infection to evaluate the relevance of antibodies against this region to the prognosis of disease. No antibodies reactive with this region were found in ELISA, indicating that this domain is not immunogenic in humans.
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PMID:Murine monoclonal antibodies directed against the transmembrane protein gp41 of human immunodeficiency virus type 1 enhance its infectivity. 137 82

A peptide designated DP-107 was synthesized containing amino acid residues 558-595 of the envelope glycoprotein gp160 of human immunodeficiency virus type 1 strain LAI (HIV-1LAI). Algorithms for secondary structure have predicted that this region of the envelope transmembrane protein should form an extended alpha-helix. Consistent with this prediction, analysis by circular dichroism (CD) indicated that, under physiological conditions, DP-107 is approximately 85% helical. The high degree of stable secondary structure in a synthetic peptide of this size suggests self-association typical of a coiled coil or leucine zipper. In biological assays, the peptide efficiently blocked virus-mediated cell-cell fusion processes as well as infection of peripheral blood mononuclear cells by both prototypic and primary isolates of HIV-1. A single amino acid substitution in the peptide greatly destabilized its solution structure as measured by CD and abrogated its antiviral activity. An analogue containing a terminal cysteine was oxidized to form a dimer, and this modification lowered the dose required for antiviral effect from 5 to about 1 microgram/ml. These results suggest that both oligomerization and ordered structure are necessary for biological activity. They provide insights also into the role of this region in HIV infection and the potential for development of a new class of antiviral agents.
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PMID:A synthetic peptide inhibitor of human immunodeficiency virus replication: correlation between solution structure and viral inhibition. 143 43

Soluble forms of a human cell-surface molecule expressed on T lymphocytes (CD4) neutralize diverse strains of both human (HIV) and simian (SIV) immunodeficiency viruses through the induction of envelope shedding and direct competition with cellular CD4 for virus binding. However, we have previously shown that sCD4 enhances infection of simian immunodeficiency viruses from African green monkeys (SIVagm) and have theorized that this enhancement is due to the induction of conformational changes leading to viral fusion (receptor-mediated activation). In this report, we compared the relative association of the envelope glycoproteins of SIVagm with HIV type 1 (HIV-1) in order to determine if a more stable association of SIVagm envelope glycoproteins might account for the differential effects of sCD4 on the infectious process. Monospecific antisera to each of the SIVagm glycoproteins were generated and used to detect stable heterodimers by radioimmunoprecipitation. Standard solubilization buffers containing both ionic and nonionic detergents or saturating concentrations of sCD4 failed to disrupt SIVagm gp120 interactions with the transmembrane protein, gp36, whereas HIV-1 heterodimers were easily dissociated. Higher concentrations of SDS (1%) were necessary to disrupt the SIVagm envelope complexes demonstrating the existence of strong noncovalent interactions between these membrane glycoproteins. In addition, morphometric analysis by electron microscopy revealed that the linear density of SIVagm spikes was stable and resisted shedding when virus was incubated with sCD4 whereas a significant decrease in linear spike density was noted for HIV-1. Based on our original hypothesis, the strong association of SIVagm glycoprotein spikes during soluble receptor binding may allow for highly stable conformational intermediates important for viral fusion, while neutralization of HIV-1 by sCD4 results from less stable envelope associations.
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PMID:Strong association of simian immunodeficiency virus (SIVagm) envelope glycoprotein heterodimers: possible role in receptor-mediated activation. 149 51

In this study the humoral antibody response in visna-maedi virus disease in sheep during long-term infection was analyzed utilizing immunoblot assays, neutralization tests and complement fixation tests. In immunoblot assays antibodies to several virus specific protein bands were detected, both against the viral envelope glycoproteins and internal proteins of the virus. The immunoblot reaction pattern resembled that found in HIV-1 infection in humans, consistent with reported similar molecular weight of the major proteins of these two viruses. The immunoblot band pattern was compared with the pattern of complement fixing and neutralizing antibodies through the preclinical and clinical course in natural and experimental cases of visna-maedi. Of six immunoblot bands identified as virus specific, the antibody response against three gag products and the major env glycoprotein appeared early in infection, at a similar time as the complement fixing antibodies. The response against two proteins, one presumably the transmembrane protein and the other possibly a gag precursor, was delayed.
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PMID:Comparison of immunoblots with neutralizing and complement fixing antibodies in experimental and natural cases of visna-maedi. 155 Apr 97

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

Although the mechanism responsible for HIV-1 entry into susceptible CD4+ T cells is incompletely understood, a number of key components are now known. For example, the tropism of HIV-1 for cells expressing the CD4 membrane glycoprotein reflects the use of this protein as a specific viral receptor to which the HIV-1 gp120 envelope protein binds with high affinity. This binding apparently results in the exposure of hydrophobic domains of the gp41 transmembrane protein to apposing plasma membrane components, resulting in the fusion of viral and plasma membranes to one another which, in turn, releases HIV-1 RNA into the cytosol. This fusion event, which is requisite for viral entry as well as HIV-1 associated syncytia formation, occurs in a pH-independent fashion, but requires antecedent T cell activation. In the absence of T cell stimuli, resting CD4+ cells are resistant to HIV-1 entry, which may explain the observation that at any given time the vast majority of CD4+ T cells in HIV-1 seropositive patients are not infected despite the presence of relatively large quantities of free virus in the blood of such patients. The mechanism of HIV-1 entry into other CD4+ cell types, such as macrophages and dendritic cells, remains to be determined.
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PMID:Mechanism of HIV-1 entry into CD4+ T cells. 168 57

The human IgG subclass response to epitopes of gp41, the transmembrane protein of HIV-1, was characterized. Twenty sera that reacted with a synthetic peptide, residues 583-599 of the env product, were analyzed in subclass-specific enzyme immunoassays with this and three other peptides: the inverted sequence (599-583; HIV-env:inv), an overlapping sequence (586-606), and one derived from the 3' end of the env gene (848-863). Also, the IgG subclass reactivities with the 583-599, 586-606 and 604-625 sequences of sera from 38 patients in various stages of HIV infection were studied. IgG1 was the most prevalent subclass. Most of the few IgG2-IgG4 reactions occurred with the peptide of the strongest antigenicity, HIV-env 604-625. The sera with detectable IgG2-IgG4 reactivity were titered to allow subclass comparisons in regions below absorbance plateaus. Two sera showed proportionately higher IgG3 relative to total IgG reactivity with HIV-env 583-599 than with HIV-env 586-606, which is indirect evidence that distinct antibody populations in these sera recognize these overlapping peptide sequences. Individual differences in the antibody response to this region may affect the immunologic control of the virus. Isotype analyses can contribute to dissection of these individualities, as shown here. High IgG reactivity with HIV-env 583-599, which was linked to absence of symptoms, resided largely in the IgG1 subclass. We found no other unambiguous association between clinical status and any IgG subclass pattern.
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PMID:Differential IgG subclass responses to epitopes in transmembrane protein of HIV-1. 169 31

A highly conserved region of the transmembrane protein gp41 of the HIV-1 was found in which the amino acid sequence 606 to 620 was characterized as an immunodominant region. The binding behaviours of a human monoclonal antibody and of polyclonal specific antibodies in sera of HIV-infected persons to this particular sequence have been studied. In two sandwich-type ELISAs with synthetic peptides as antigen representing this region, sera of 312 HIV-infected persons at all stages could be clearly discriminated against 500 anti-HIV antibody negative sera of healthy blood donors.
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PMID:Binding behaviour of antibodies reacting specifically with an immunodominant region of the transmembrane protein gp41 of HIV-1. 169 22


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