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Query: UMLS:C0001175 (AIDS)
 120,706 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The in vitro suppressive effect of gp120 and gp120/anti-gp120 antibody is well known but not yet proven to operate in vivo. We report findings consistent with the presence of gp120/anti-gp120 antibody complexes on CD4+ lymphocytes from HIV-infected patients with advanced disease. PBMC from most AIDS patients showed selective masking of the CD4 epitope associated with the gp120 binding site; immunoprecipitation of PBMC with anti-CD4 mAb disclosed high amounts of IgG bound to CD4 receptors. Antibodies against HIV env proteins, but not other HIV products or CD4 Ag, were detected in purified CD4+ cell culture supernatants; in vitro culture was associated with normalization of both CD4 expression in PBMC and the lymphocyte proliferative response to anti-CD3. gp120 presence could not be directly demonstrated, but findings strongly suggested that CD4+ lymphocytes from most HIV-infected patients with advanced disease were covered with gp120/anti-gp120 antibody complexes, which are responsible for down-regulation of surface CD4 expression as well as functional lymphocyte impairment; this event may represent an important mechanism in the pathogenesis of HIV-associated immunodeficiency.
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PMID:CD4 epitope masking by gp120/anti-gp120 antibody complexes. A potential mechanism for CD4+ cell function down-regulation in AIDS patients. 137 95

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

Immunization of mice and rats with purified external glycoprotein gp120 from two divergent human immunodeficiency virus type 1 (HIV-1) isolates resulted in the development of seven hybridomas secreting monoclonal antibodies able to recognize regions of gp120 which are common among divergent strains of HIV-1. These monoclonal antibodies cross-reacted with env glycoproteins from one African (Rutz), one Haitian (RF), and three North American viral isolates, namely IIIB, MN, and 451 by either immunoblot or radioimmunoprecipitation assays. All recognized denatured gp120 in immunoblots with the exception of one which required a conformationally intact glycoprotein for reactivity. The gp120 epitopes identified by these antibodies were mapped by screening of an env gene library in the lambda gt11 expression system. Three out of four epitopes were found to reside in the amino-terminal half of gp120 (Cys9 to Cys35, Thr44 to Glu72 and Val108 to Met130), the other was located in the middle region (Thr221 to Ser255). By virtue of their extent of cross-reactivity these reagents might provide a unique resource for the detection of new viral isolates related to HIV-1.
AIDS Res Hum Retroviruses 1992 Jun
PMID:Delineation of immunoreactive, conserved regions in the external glycoprotein of the human immunodeficiency virus type 1. 138 Feb 59

The env polyprotein sequences of several simian immunodeficiency virus (SIV) isolates were analyzed using computer algorithms designed to predict immunologically reactive protein segments. Peptides corresponding to predicted epitopes were synthesized and employed in peptide enzyme-linked immunosorbent assay (ELISA) screening of serum panels from experimentally infected macaques, as well as naturally infected, asymptomatic mangabeys and African green monkeys. Several of the peptides are recognized by a high percentage of antisera from each panel of monkeys indicating that they represent group-specific antigenic determinants of SIV. Several type-specific determinants also were identified. These peptides may be a useful tool for studying the kinetics of SIV glycoprotein-specific immune responses produced by infected and vaccine-protected monkeys at the epitope level.
AIDS Res Hum Retroviruses 1992 Jun
PMID:Identification of broadly reactive continuous antigenic determinants of simian immunodeficiency virus glycoproteins. 138 Feb 62

The development of AIDS-related lymphomas (ARL) has been on the rise in recent years. During an analysis of ARL from AIDS patients, one individual developed atypical syncytial variants of high-grade Burkitt's-type B-cell lymphomas, which prompted further study. However, the search for a HIV-1 retrovirus, which we hypothesized was infecting these cells, led to the subsequent discovery of a type D retrovirus in two early-passage lymphoma cell lines derived from this patient. Nucleotide and amino acid sequence analysis, as well as immunologic reactivity, indicated that the virus was closely related to Mason-Pfizer monkey virus (MPMV) or simian retrovirus type 1 (SRV-1). MPMV and SRV-1 are immunosuppressive type D retroviruses that cause an AIDS-like syndrome in rhesus macaques. Amplification of DNA from the patient's diagnostic bone marrow biopsy specimen by the polymerase chain reaction generated MPMV-specific fragments indicative of infection by a retrovirus similar to MPMV. Additionally, the patient's serum contained antibodies that recognized type D retroviral env proteins (gp20 and gp70) and gag proteins (p27 and p14) as assayed by immunoblot and radioimmunoprecipitation techniques. Although there have been reports of human cell lines infected with type D retroviruses and of type D reactive human sera, this is the first report of a type D retrovirus infection in a human confirmed by virus isolation, serum immunoreactivity, and viral DNA identification in tumor tissue.
AIDS Res Hum Retroviruses 1992 May
PMID:Studies on a type D retrovirus isolated from an AIDS patient lymphoma. 138 Dec 7

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

Recombinant human adenoviruses (Ads) that replicate in the intestinal tract offer a novel, yet practical, means of immunoprophylaxis against a wide variety of viral and bacterial pathogens. For some infectious agents such as human immunodeficiency virus (HIV), the potential for residual infectious material in vaccine preparations must be eliminated. Therefore, recombinant human Ads that express noninfectious HIV or other microbial proteins are attractive vaccine candidates. To test such an approach for HIV, we chose an experimental model of AIDS based on simian immunodeficiency virus (SIV) infection of macaques. Our data demonstrate that the SIV Env gene products are expressed in cultured cells after infection with a recombinant Ad containing both SIV env and rev genes. An E3 deletion vector derived from a mutant of human Ad serotype 5 that efficiently replicates in both human and monkey cells was used to bypass the usual host range restriction of Ad infection. In addition, we show that the SIV rev gene is properly spliced from a single SIV subgenomic DNA fragment and that the Rev protein is expressed in recombinant Ad-SIV-infected human as well as monkey cells. The expression of SIV gene products in suitable live Ad vectors provides an excellent system for studying the regulation of SIV gene expression in cultured cells and evaluating the immunogenicity and protective efficacy of SIV proteins in macaques.
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PMID:Coexpression of the simian immunodeficiency virus Env and Rev proteins by a recombinant human adenovirus host range mutant. 140 12

In order to examine the potential role of env-induced membrane fusion in the cytopathogenic properties of HIV-1 in cell culture, the effects of mutations within the proteolytic cleavage site of gp160, which result in a reduction but not a complete absence of proteolytic processing have been further studied. Cells expressing the mutant glycoproteins were shown to be severely reduced in their capacity to form syncytia. However, viruses encoding these glycoproteins could infect cell culture cells, albeit with delayed kinetics, and, at late infection time points, resulted in complete cytolysis of the infected culture. Since amplification by polymerase chain reaction and direct sequencing of the DNA in the infected cultures confirmed the presence of the mutant and the absence of revertant DNA, this shows that the amount of fusion competent viral glycoprotein does not influence HIV-1 cytopathogenicity, but rather that other parameters must be involved in inducing cell death.
AIDS Res Hum Retroviruses 1992 Oct
PMID:HIV-1-induced cytopathogenicity in cell culture despite very decreased amounts of fusion-competent viral glycoprotein. 145 94

A recently developed sensitive assay to examine the early stages of HIV-1 env-mediated cell fusion is based on the redistribution of fluorescent dyes between membranes and cytoplasm of adjacent cells, monitored by fluorescence video microscopy. This assay demonstrated that membrane fusion can occur under conditions where no syncytia are formed. Fusion started earlier than syncytia formation and was not very sensitive to HIV-1 env+/CD4+ cell ratios. In the current study, this assay was used to determine the role of LFA-1 in HIV-1 env-mediated membrane fusion and syncytia formation. CD4- LFA-1- Epstein-Barr virus transformed lines from two leukocyte adhesion deficiency patients were infected with recombinant vaccinia expressing gp120/41 (HIV-IIIB), and cocultured with CD4+ subclones of the human T cell line CEM, which were generated by chemical mutagenesis and express either normal (LFA-1+), or low levels of LFA-1 (LFA-1lo). It was found that the LFA-1lo T-cell clone formed much smaller and fewer syncytia compared to the LFA-1+ subclones, but both clones fused equally well with the gp120/41 expressing LFA-1- B cells as monitored by redistribution of fluorescent dyes. Furthermore, monoclonal antibodies against the LFA-1 molecules reduced the number of syncytia formed but had no effect on membrane fusion. These findings demonstrate that the adhesion molecule LFA-1 does not play a crucial role in the early events of HIV-1 env-mediated cell membrane fusion, but may contribute to the later events leading to giant cell formation.
AIDS Res Hum Retroviruses 1992 Sep
PMID:LFA-1 adhesion molecules are not involved in the early stages of HIV-1 env-mediated cell membrane fusion. 145 5


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