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

In a study population representing different CDC stages of HIV infection, 58% exhibited IgA hypergammaglobulinemia resulting from proportional increases in both the IgA1 and the IgA2 subclasses. These increases were detected early in infection, did not correlate with CD4 count, and remained elevated throughout disease progression. Absolute concentrations of polymeric IgA present within each subclass were unchanged, indicating that increased production of monomeric IgA1 and IgA2 were responsible for elevations of total IgA. These elevations were not completely attributable to a specific antibody response to viral infection, since Western blot analysis of purified IgA samples indicated that HIV-reactive IgA antibodies could be demonstrated only within the IgA1 subclass. Dominating IgA1 anti-HIV responses were also observed in two secretory IgA samples isolated from colostrum of healthy HIV seropositive mothers, suggesting that a similar isotype restriction exists in the mucosal IgA compartment. The binding of IgA1 to HIV proteins contrasted markedly to that observed with identical concentrations of IgG purified from the sera of the same patients. While IgG reacted more intensely and broadly with all HIV proteins, IgA1 antibodies were directed predominantly against envelope glycoproteins. In many patients, a total lack of IgA1 reactivity to gag and pol proteins was accompanied by intact IgG responses to these same antigens. Though all IgA samples examined reacted with HIV, fewer responses to gp160, gp120, and p24 were observed in samples from AIDS and AIDS-related complex (ARC) patients, suggesting a declining titer of IgA antibodies against these antigens may be associated with disease progression.(ABSTRACT TRUNCATED AT 250 WORDS)
AIDS Res Hum Retroviruses 1992 Oct
PMID:Serum IgA subclasses and molecular forms in HIV infection: selective increases in monomer and apparent restriction of the antibody response to IgA1 antibodies mainly directed at env glycoproteins. 145 91

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

Human immunodeficiency virus (HIV) membrane has been reconstituted from the recombinant envelope glycoprotein precursor (gp160) by a detergent dialysis technique. Electron microscopy shows that gp160-virosomes are spherical vesicles with a mean diameter identical to that of viral particles. Enzyme-linked immunosorbent assay and immunogold labeling demonstrate efficient association of gp160 with lipid vesicles and proteolysis treatment reveals an asymmetric insertion with about 90% of glycoproteins having their gp120-moiety pointing outside. Glycoproteins are organized as dimers and tetramers and gp160 retains its ability to specifically bind CD4 receptor after reconstitution into virosome.
AIDS Res Hum Retroviruses 1992 Oct
PMID:Properties of HIV membrane reconstituted from its recombinant gp160 envelope glycoprotein. 145 95

Mutations within the principal neutralizing determinant (the V3 loop) of the HIV-1 surface envelope glycoprotein gp120 block or greatly reduce the ability of the HIV-1 envelope glycoprotein to induce cell fusion in CD4+ HeLa T4 cells while keeping its CD4 binding ability. However, when either cysteine or both cysteines forming the V3 disulfide bridge were mutated, the resultant glycoprotein could not mediate cell fusion, undergo proteolytic processing, or bind CD4. To investigate the role that the V3 loop plays in gp160 processing and CD4 binding, we deleted the entire V3 loop region of the HIV-1 env gene. The resultant glycoprotein could not mediate cell fusion in the HeLa T4 cell line and no proteolytic processing of gp160 or CD4 binding could be detected. To test whether any domain of the V3 loop is involved in attaining the proper envelope glycoprotein conformation required for proteolytic processing and CD4 binding, we introduced a series of deletions into the coding region of the V3 loop. Most of the residues within the V3 loop could be removed while retaining gp160 processing and CD4 binding. Our results indicate that the cysteines that form the V3 loop or the disulfide bond itself are important for proper envelope glycoprotein folding and processing. Because many of the mutants constructed in this study do not contain the type-specific neutralizing determinant of HIV-1, they may be potential reagents to bind group-specific neutralizing antibodies or to elicit a group-specific neutralizing response against HIV-1.
AIDS Res Hum Retroviruses 1992 Sep
PMID:Studies on the role of the V3 loop in human immunodeficiency virus type 1 envelope glycoprotein function. 145 7

A highly purified saponin from Q. saponaria (QS-21) was tested in juvenile rhesus macaques for adjuvant activity and toxicity. The QS-21 was tested alone or as part of an experimental subunit HIV-1 vaccine containing a truncated recombinant HIV-1 envelope protein (gp160D) adsorbed to alum. Antibody responses were measured using ELISA and cell-mediated immunity was measured using cellular proliferation assays. Potential toxicity was monitored by standard clinical pathology testing using peripheral blood and urine samples. No toxic effects were observed, even after the administration of the experimental vaccines three times at monthly intervals. The QS-21 saponin adjuvant enhanced total antibody production levels by greater than 100-fold and broadened the specificity of the response so that additional epitopes were recognized, when compared with alum-adsorbed HIV-1 gp160D formulation. Low-level, antigen-specific proliferative responses to HIV-1 recombinant gp160 were induced by either vaccine formulation. Proliferative responses were induced by a sham challenge with soluble recombinant HIV-1 gp160 for all of the animals that had been vaccinated. However, those that received the HIV-complete vaccine formulation containing QS-21 responded significantly better. These data demonstrated that the QS-21 adjuvant augmented both antibody responses and cell-mediated immunity and established immunological memory. The potent adjuvant activity and lack of toxicity suggest that this adjuvant should be safe and effective for use in HIV-1 vaccines.
AIDS Res Hum Retroviruses 1992 Aug
PMID:Immunogenicity and toxicity testing of an experimental HIV-1 vaccine in nonhuman primates. 146 70

The effectiveness and security of azidothymidine (AZT) in the treatment of patients with infection by the human immunodeficiency virus (HIV) and persistent generalized adenopathies (PGA), were assessed. Thirty six patients with HIV infection and PGA participate in the study. Eighteen were treated with AZT and the other 18 were included in the control group, since they did not accept the treatment. Both groups were homogeneous with respect to their clinical, immunological and virological characteristics. A common study protocol was used and the clinical, immunological and virological effectiveness was assessed. Lymphocyte subpopulations were quantified by flow cytometry, viral antigens were determined by sandwich-type ELISA and antibodies against viral proteins (anti-gp120, anti-gp160, anti-gp41, anti-gp24 and anti-p18) were detected by Western blot. Naranjo and Busto's algorithm was used for the causality of adverse effects. We did not observe any significant differences regarding the presence of infection and the evolution of AIDS in both groups. A positive response to thrombocytopenia was observed, more evident in patients under low doses of AZT. The small initial transitory improvement of the immunological parameters was not statistically significant. The viral antigen was not modified by the treatment. With respect to the behaviour of the several antibodies studied, no differences were observed. The initial doses of AZT had to be modified in 44% of patients due to their hematological toxicity, more frequent in the first stages of the treatment. In two patients, the treatment had to be finally discontinued due to severe neutropenia. 25% of patients showed mild to moderate gastrointestinal manifestations.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Azidothymidine in the treatment of patients with human immunodeficiency virus infection and persistent generalized adenopathies]. 146

Serosurveys conducted prior to 1988 indicated a very low level of HIV-1 infection in Thailand, even among high-risk groups. The Ministry of Health has reported a dramatic increase in HIV-1 infection during the last three years. The geographic and demographic distribution of the epidemic is broad, involving multiple provinces and risk groups. Foci of higher incidence and prevalence have been noted in the urban center of Bangkok and in the northern provinces of Chiang Mai and Chiang Rai. Here we report the results of genetic characterization of 16 HIV-1 isolates from Thailand using a combination of polymerase chain reaction (PCR) typing and DNA sequencing. The complete sequence of gp160 (env) of five isolates, partial env sequence of six additional isolates, and the gag gene of two isolates were determined. Two highly distinct HIV-1 variants were found. One variant resembled those prevalent in North America and Europe; five of the isolates were of this type. The remaining eleven isolates were very similar to one another and represented a variant unlike any previously described. Phylogenetic tree analysis of complete env and gag genes placed the two variants on widely separated branches. Protein sequence comparisons indicate both general and specific features that distinguish the Northern Thailand variant both from the Bangkok variant and from virtually all previously sequenced HIV-1 isolates. A simple PCR test for distinguishing the two variants has been developed for use in epidemiologic surveys.
AIDS Res Hum Retroviruses 1992 Nov
PMID:Genetic variants of HIV-1 in Thailand. 148 77

An SV40-based expression vector was used to generate CD4-negative murine L cell lines which stably expressed the human immunodeficiency virus envelope glycoprotein (env). Despite the presence of abundant intracellular envelope glycoprotein, the expression of env gp120/41 was not detected on the cell surface. Pulse-chase studies showed that the majority of the gp120 detected at the end of a 20-h chase was in the culture medium. Therefore gp120 was shed and/or secreted from these cells. Transfected L cells (H-2k) served as targets for specific lysis by CTL raised against vaccinia virus-encoded env gp160. The discrepancy in relative levels of intracellular versus surface expression of env was probably due to the highly inefficient processing of newly synthesized gp160, as well as the apparent instability of the gp120/41 complex in the transfected cell lines. Digestion of immunoprecipitated gp120 and gp160 with endoglycosidase H and peptide N-glycosidase F revealed that the envelope glycoprotein in transfected L cells possessed both high mannose and complex N-glycans, analogous to the posttranslational modification of the mature envelope glycoprotein in infected T cells. These studies indicate that the relatively inefficient processing of env gp160 occurs in the absence of CD4, and that the stable surface expression of envelope gp120/41 complex may require additional factors not present in transfected cells.
AIDS Res Hum Retroviruses 1992 Dec
PMID:Stable expression of the human immunodeficiency virus type 1 envelope glycoprotein in transfected L cells. 149 50

Transfection of the human CD4 molecule into mouse cells does not confer susceptibility to human immunodeficiency virus type 1 (HIV-1) infection. Expression of the human CD4 molecule in transgenic mice was seen to offer some new possibilities. However, transgenic mouse T cells expressing either the human CD4 receptor, or a hybrid human/mouse CD4 receptor alone or in conjunction with human major histocompatibility complex class I molecules, were refractory to in vitro HIV-1 infection. In addition, no infection was observed after in vivo HIV inoculation to mice of these various transgenic lines. Injection of recombinant gp160 viral protein to the transgenic mice did not alter their T and B cell populations. The existence of a dominant block in mouse cells that prevents HIV entry is discussed.
AIDS Res Hum Retroviruses 1992 Dec
PMID:Expression of human CD4 in transgenic mice does not confer sensitivity to human immunodeficiency virus infection. 149 54

We examined the sera of volunteers vaccinated with recombinant gp160 of human immunodeficiency virus type 1 (HIV-1) and control volunteers for the presence of anti-(anti-gp160 idiotype) antibodies which antigenically mimic gp160 and, therefore, bind to CD4 on human cells. Anti-CD4 antibodies were detected in the sera of 3 of 5 rgp160 recipients and 1 of 5 controls by indirect immunofluorescence using CD4-transfected HeLa cells or enzyme-linked immunosorbent assay (ELISA) using recombinant soluble CD4 as the solid phase. The control volunteer who was positive subsequently developed antibodies to HIV-1 by Western blot analysis. The anti-CD4 antibodies detected in the sera of the rgp160 vaccinees and the control volunteer appeared to be anti-idiotypic in nature, reacting with a paratope expressed on goat anti-gp160 antibodies but not on antibodies from normal goat serum. Binding to either transfected CD4+ HeLa cells or blotted anti-gp160 serum could be inhibited by preincubating the anti-CD4 serum with soluble CD4, or preincubating the cells or blotted anti-gp160 serum with recombinant gp160. Anti-CD4 antibodies were initially detectable only after the antibody response to gp160 began to decrease in the vaccinees, and the HIV-1-infected volunteer mounted a detectable anti-HIV-1 antibody response only after a decline in the anti-CD4 antibodies in his serum. These data strongly suggest that anti-CD4 antibodies which are anti-idiotypic to a paratope expressed on anti-gp160 antibodies are generated in response to both vaccination with rgp160 and infection with HIV-1.(ABSTRACT TRUNCATED AT 250 WORDS)
AIDS Res Hum Retroviruses 1992 Jun
PMID:Anti-CD4 anti-idiotype antibodies in volunteers immunized with rgp160 of HIV-1 or infected with HIV-1. 150 23


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