Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0001175 (AIDS)
 120,706 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Ten monoclonal antibodies prepared against a soluble, recombinant form of gp160, derived from the IIIB isolate of HIV-1, were characterized. Four of the antibodies neutralized HIV-1IIIB infectivity in vitro, three blocked the binding of recombinant gp120 to CD4, three were reactive with gp41, and one preferentially reacted with an epitope on gp120 within the gp160 precursor. All three CD4 blocking antibodies bound to distinct epitopes, with one mapping to the C1 domain, one mapping to the C4 domain, and one reactive with a conformation-dependent, discontinuous epitope. Of these, the antibody reactive with the discontinuous epitope exhibited neutralizing activity against homologous and heterologous strains of HIV-1. The binding of these monoclonal antibodies to a panel of seven recombinant gp120s prepared from diverse isolates of HIV-1 was measured, and monoclonal antibodies with broad cross reactivity were identified. The epitopes recognized by 7 of the 10 monoclonal antibodies studied were localized by their reactivity with synthetic peptides and with fragments of gp120 expressed as fusion proteins in a lambda gt-11 gp160 epitope library.
AIDS Res Hum Retroviruses 1992 Nov
PMID:Monoclonal antibodies to the extracellular domain of HIV-1IIIB gp160 that neutralize infectivity, block binding to CD4, and react with diverse isolates. 128 8

Two antibodies, affinity-purified from human immunodeficiency virus-positive human plasma with synthetic peptides in the region gp41(566-596), were found to recognize oligomeric gp41 more strongly than the monomeric form in an immunoblot assay. In contrast, a murine anti-gp160 monoclonal antibody, which maps within this sequence to gp41(581-596), recognized only monomeric gp41 after disruption of the oligomer with sodium dodecyl sulfate. This monoclonal anti-gp160 antibody did not recognize chemically crosslinked oligomeric gp41 that had been treated with similar conditions used to disrupt the gp41 oligomer. These results indicate that this epitope is inaccessible to binding by this antibody when gp41 is oligomeric. Cyanogen bromide cleavage of gp41 resulted in a 17-kD fragment Thr-541-Met-631. A significant proportion of this fragment was oligomeric when derived from chemically crosslinked gp41. The region Ala-566-Gln-596, within the cyanogen bromide fragment, contains the oligomerization-sensitive epitopes as well as two lysine residues available for crosslinkage. This region is relatively conserved and has the propensity to form an amphipathic alpha-helix.
AIDS Res Hum Retroviruses 1992 Dec
PMID:Antibody epitopes sensitive to the state of human immunodeficiency virus type 1 gp41 oligomerization map to a putative alpha-helical region. 128 26

In the first AIDS vaccine trial, immunizing preparations were based on HIV-1 Env protein (gp160). Immunogenic properties of gp160 which trigger both a humoral and cellular immune response have since justified its use in various vaccine programs, both past and present. Many reports however have underlined deleterious effects on the immune system--anti-HIV-1 enhanced antibodies, anti-CD4 autoantibodies, and inhibition of T cell activation by HIV-1--particularly associated with the Env protein. The present study shows that gp160 presented in a biologically inactivated but immunogenic form, as used in our trial, could avoid these complications. Bio-hazards associated with gp160 which indeed could be removed by appropriate treatment of the native protein, should be taken into consideration in AIDS vaccine programs.
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PMID:Removal of gp160 induced bio-hazards for a safe AIDS vaccine candidate. 129 45

Out of a total of 1,600 foreign students who came to India between June 1989 and October 1990, 22 were seropositive for HIV-1. Ten showed antibodies to all the gene products. Antibodies to gp160 and p24 were present in all the seropositives while antibodies to p53, p15/17 were significantly higher in healthy seropositives than in patients with full blown AIDS. Absence of antibodies to p15/17 and p53 thus appeared to be a more sensitive criterion of end stage disease than absence of anti- p24 antibodies. When seropositive samples from African students were checked for HIV-2 antibodies by ELISA, 13/22 were found to be positive. Further, 2/10 Indians with full blown AIDS were also strongly positive for HIV-2. These data could be of relevance for formulating future strategies for population-based screening for HIV-2.
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PMID:Comparative evaluation of HIV infected foreign students and Indian with AIDS in Chandigarh, India. 130 16

The bestfit computer program was used to compare the amino acid sequence of the gp160 envelope glycoprotein of an apathogenic AGM and the pathogenic SIVAGM monkey lentiviruses. It was found that the gp120 envelope glycoproteins of these viruses resembled each other in their functional domains. However, an insert of 40 amino acids was found in the gp41 envelope glycoproteins of the pathogenic SIVAGM virus in the amino acid sequence between the membrane anchoring sequence and the carboxyterminus. The insert introduced a new "RRIR" proteolytic cleavage signal into gp41. Comparing HIV-1 gp41 to that of the pathogenic SIVAGM virus revealed that the HIV-1 sequence contains an "RR" sequence that also serves as a signal for proteolytic cleavage. Comparing HIV-2 gp41 to the apathogenic and pathogenic simian immunodeficiency viruses revealed that HIV-2 gp41 lacks the above proteolytic cleavage signal. It is hypothesized that the pathogenic human and simian immunodeficiency lentiviruses can be proteolytically cleaved at the carboxyterminus of gp41, releasing two peptides: a) an "immunodeficiency" 58 amino acid peptide and b) an IL-2-like peptide. The apathogenic AGM virus and the less pathogenic HIV-2 lack one proteolytic cleavage signal in the gp41 amino acid sequence and therefore can release only the IL-2-like peptide but not the "immunodeficiency" peptide. If indeed the pathogenic SIVAGM and HIV-1 do release an "immunodeficiency" peptide, then such a peptide can be regarded as a toxin. Immunization of healthy individuals or HIV-1 patients against the toxic effect of the viral gp41 toxic peptide might prevent damage to the immune system when the virus reactivation leads to ARC and AIDS in infected individuals. Synthetic peptides modeled according to the immunodeficiency peptide (the toxin) can be used to produce anti-toxin antibodies in healthy HIV-1 infected individuals. Such anti-toxin antibodies can be used for passive immunization of AIDS patients or for active immunization of HIV-1 positive individuals prior to ARC or AIDS.
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PMID:Computer analysis of the amino acid sequences in gp41 of apathogenic African green monkey (AGM) virus, less pathogenic HIV-2 and highly pathogenic SIV and HIV-1 lentiviruses. 133 29

Two distinct regions or epitope clusters of human immunodeficiency virus type 1 (HIV-1) gp120 have been shown to elicit neutralizing antibodies: the V3 loop and the CD4-binding site. We have isolated neutralizing human monoclonal antibodies (HuMAbs) against conserved epitopes in both of these regions. In this study, we demonstrate that an equimolar mixture of two of these HuMAbs, one directed against the V3 loop and the other against the CD4-binding site, neutralizes HIV-1 at much lower concentrations than does either of the individual HuMAbs. Mathematical analysis of this effect suggests cooperative neutralization of HIV-1 by the two HuMAbs and demonstrates a high level of synergy, with combination indices (CIs) of 0.07 and 0.16 for 90% neutralization of the MN and SF-2 strains, respectively. The dose reduction indices (DRIs) for each of the two HuMAbs at 99% neutralization range approximately from 10 to 150. A possible mechanism for this synergism is suggested by binding studies with recombinant gp160 of the MN strain; these show enhanced binding of the anti-CD4 binding site HuMAb in the presence of the anti-V3 loop HuMAb. These results demonstrate the advantage of including both V3 loop and CD4-binding site epitopes in a vaccine against HIV-1 and indicate that combinations of HuMAbs against these two sites may be particularly effective in passive immunotherapy against the virus.
AIDS Res Hum Retroviruses 1992 Apr
PMID:Synergistic neutralization of HIV-1 by human monoclonal antibodies against the V3 loop and the CD4-binding site of gp120. 137 35

Cellular immunogenicity of env gp160, nef p27, and gag p55 proteins of human immunodeficiency virus type 1 (HIV-1) was studied in mice immunized with vaccinia virus recombinants. Proliferative responses of spleen cells were comparable against env gp160, nef p27, and gag p25 recombinant proteins. No specific activity was observed against gag p18 protein. Env, nef, and gag-specific T-cell lines were generated by repeated stimulation of immune spleen cells with recombinant HIV-1 proteins. They were CD4 positive, proliferative, and also cytotoxic against HIV-transfected target cells. Specificity of the T-cell response against nef and gag protein was analyzed with synthetic peptides. Peptides nef 15, nef 16, and gag AM-30 were, respectively, reactive in nef- and gag-specific proliferative and cytolytic assays. The three peptides described have a relatively conserved amino acid sequence among HIV isolates and appear broadly immunoreactive among species.
AIDS Res Hum Retroviruses 1992 Apr
PMID:HIV-1 env, nef, and gag-specific T-cell immunity in mice: conserved epitopes in nef p27 and gag p25 proteins. 137 36

The derivation of ethyl-methanesulfonate (EMS) mutagenized subclones from the CEM T-cell line has been described. These clones expressed CD4 and bound soluble gp120, however, two of the generated clones were markedly reduced in their ability to form syncytia after infection with either gp160-vaccinia vector or cell-free human immunodeficiency virus type 1 (HIV-1). Here, we asked at what stage(s) viral infection is blocked in these cells. Polymerase chain reaction (PCR) analysis revealed that at 6 and 72 h postinfection with HIV-1, cells of the syncytia-deficient clones expressed markedly reduced amounts of viral-specific DNA compared with cells of the parental line or the syncytia-positive clones. Long-term cultures revealed a marked delay in the appearance of reverse transcriptase (RT) activity in the supernatants of these subclones when compared with the parental line and viral replication did not lead to massive cell death. Syncytia formation in HIV-1-infected cultures of the syncytia-deficient subclones was enhanced by tumor necrosis factor alpha (TNF alpha) when added 24 h postinfection. In contrast, pretreatment with TNF alpha for 48 h followed by washing and infection of the cells with HIV-1 augmented syncytia formation of the syncytia-positive subclones, but not of the syncytia-negative subclones. Thus, the EMS-mutagenized subclones may provide a tool to study host cell factors required for the establishment of a productive HIV-1 infection and responsiveness to TNF alpha.
AIDS Res Hum Retroviruses 1992 Jun
PMID:Study of viral replication in HIV-1-infected CEM T-cell subclones which are reduced in their ability to form syncytia. 138 Feb 60

Although it is recognized that human immunodeficiency virus (HIV) env genes exhibit a high degree of variability, little is known about the molecular heterogeneity of gp120-specific antibodies in infected individuals. As a first step to approach this issue, we investigated the idiotypic relatedness of anti-gp120 antibodies present in the serum of HIV-infected individuals. Idiotypic determinants (idiotopes) are fingerprints of the variable region of the antibody molecule and, as such, they represent unique probes with which to explore the diversity of the immune response. We isolated IgG anti-gp120 antibodies from the serum of a seropositive asymptomatic individual by affinity chromatography. The purified antibodies were shown to bind gp120 and gp160 by ELISA, Western blotting and radio-immunoprecipitation. They also recognized HIV-infected human T cells as detected by immunofluorescence. Anti-idiotypic reagents were generated against this gp120 idiotype, and one of them was used to study anti-gp120 idiotypic diversity in a panel of 65 sera drawn from AIDS and AIDS-related complex patients, and from HIV seropositive asymptomatic individuals. Sixty normal human sera were used as negative controls. We found no evidence for common idiotopes on anti-gp120 antibodies of unrelated individuals. In contrast, we also noticed that the idiotypic profile expressed sequentially at two different intervals in a persistently infected individual showed little variation. Finally, when the diversity of murine anti-gp120 antibodies with a monoclonal anti-idiotype was analysed, no evidence of cross-reactive idiotopes in the murine system was found.
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PMID:Idiotypic expression of anti-gp120 antibodies in unrelated human immunodeficiency virus-infected individuals. 138 96

Human immunodeficiency virus (HIV) has been implicated as the etiologic agent of acquired immunodeficiency syndrome and is a member of the sub-family Lentivirinae within the family Retroviridae. HIV type 1 (HIV-1) contains three major genes, gag, pol and env, which code for (1) core proteins, (2) a protease, reverse transcriptase and integrase, and (3) envelope glycoproteins, respectively. The core proteins p17, p24 and p15 are derived from gag precursor, p55, by endoproteolytic cleavage. The two nucleic-acid-binding proteins p7 and p9 are synthesized from p15 by proteolytic cleavage. These two structural proteins are apparently needed for the ribonucleoprotein-core formation. The envelope glycoproteins gp120 and gp41 (gp120-gp41 complex) are also generated by cleavage env precursors, gp160. The assembly of HIV-1 particles, like other retroviruses, appears to involve the association of the env precursor gp160 with the gag proteins. There are several factors which influence the assembly and budding process of HIV-1. In this article, we describe important events in HIV-1 morphogenesis and factors which influence this aspect of the HIV-1 life cycle.
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PMID:Morphogenesis of human immunodeficiency virus type 1. 138 14


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