Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019693 (HIV)
 170,526 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Reductions in the percentage and absolute number of CD4+ lymphocytes, as well as abnormally high levels of activated peripheral T lymphocytes (CD3+ HLA-DR+ phenotype) and an increased proportion of CD8+ cells coexpressing the CD57 surface antigen (involved in natural killer activity) have been reported in HIV infection and associated with disease progression. We prospectively measured these subsets of lymphocytes in 34 patients with advanced AIDS-related complex (ARC) treated with azidothymidine (AZT). Peripheral blood lymphocyte phenotyping was performed before treatment, then at weeks 12 and 24. A striking fall in the proportion of activated T lymphocytes from baseline was observed (P less than 0.001) at week 24. In contrast, the percentage of CD4+ cells showed a slight and transient rise at week 12 (P less than 0.05). No modification in levels of CD8+ or CD8+ CD57+ cells was detected during the study. Of the 34 patients, 11 developed AIDS, and 23 remained AIDS-free during 51 weeks of follow-up. Similar patterns of change in CD4+ and HLA-DR+ CD3+ lymphocytes were found in the AIDS progressors and nonprogressors. Likewise, HIV p24 antigenaemia showed parallel decreases in both groups of patients. Although changes in CD4+ cells, p24 antigenaemia and HLA-DR-reactive T lymphocytes were not predictive of clinical outcome, large differences existed between the two groups prior to the initiation of therapy. The short-term onset of AIDS was associated with lower CD4+ cell numbers, higher levels of serum p24 antigen and a greater proportion of activated T lymphocytes. Our results suggest that the possible interest of T lymphocyte activation markers, in conjunction with conventional phenotyping, should be investigated further.
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PMID:T activation marker evaluation in ARC patients treated with AZT. Comparison with CD4+ lymphocyte count in non-progressors and progressors towards AIDS. 169 59

In order to identify the target epitopes recognized by specific CTL in the NEF protein of HIV-1, 33 peptides derived from the HIV-BRU sequence were tested with NEF-specific CTL generated from HIV-seropositive donors. Six different epitopes were identified and several points were remarkable: 1) They were all located in two regions of the central part of the NEF protein corresponding to residues 73 to 94 and 113 to 147, respectively. 2) The CTL issued from a single donor could recognize several peptides of the NEF protein. 3) Some of these peptides could be recognized in association with at least two or three different HLA class I molecules. 4) Two different overlapping epitopes were present in a relatively short sequence of 15 amino acids. These results suggest that multiple epitopes corresponding to different HLA restrictions could coexist in a relatively small region of the NEF protein. The implications of these results in vaccine strategies using synthetic peptides bearing CTL epitopes are discussed.
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PMID:Six epitopes reacting with human cytotoxic CD8+ T cells in the central region of the HIV-1 NEF protein. 170 97

This study investigated the effects of PMA on biosynthesis and transcription of the CD4 molecule and gene in order to define mechanisms resulting in reduced cell surface expression of the CD4 molecule after treatment with PMA. Cells treated with PMA showed reduced biosynthesis of the CD4 molecule but not of class I HLA molecules. Furthermore, PMA treatment resulted in reduced steady-state levels of CD4 mRNA and inhibition of the relative rate of transcription of the CD4 gene. Cells expressing transfected CD4 cDNA gene products modulated in response to PMA, however, re-expressed CD4 earlier than cells expressing the product of the wild-type CD4 gene. These data suggest that the cell surface expression of the CD4 molecule is probably down-regulated at the level of the protein, as well as the gene, and that inhibition of transcription may affect the kinetics of CD4 expression. These observations provide further insight into the mechanisms by which HIV affects expression of CD4.
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PMID:Phorbol esters down-regulate transcription and translation of the CD4 gene. 170 23

Previously we showed that over 50% of CD8 cells from HIV-infected persons do not survive in 3-day cultures of mononuclear cells; this loss occurred preferentially in subsets with phenotypes indicative of in vivo activation. In the studies reported here, we asked if cytokines enhanced CD8 cell survival. Of IL1, IL2, IL4, IL6, tumor necrosis factor, and interferon-gamma only IL2 specifically enhanced CD8 survival in the HIV group, compared to the control group. Further studies thus focused on characterizing CD8 cell survival in the presence of IL2. In both study groups, three subsets of CD8 cells were identified based on in vitro survival: (a) those surviving in culture medium alone (survivors), (b) those surviving only when IL2 was included in the culture medium (IL2-dependent survivors), and (c) those failing to survive even in the presence of IL2 (nonsurvivors). By dual-color cytofluorometry, the CD8 survivor subset was similar in the two study groups, and expressed nonactivated phenotypes (Leu8+, CD45RA+, HLA-DR-). The IL2-dependent survivor subset was also similar in the two study groups and expressed the phenotypes Leu8-, CD45RA+, CD57+, HLA-DR+, and CD38+, suggesting prior activation. The CD8 nonsurvivor subset, in contrast, was markedly different in the study groups: compared to the control group, the HIV group contained significantly higher proportions of CD8 cells expressing the phenotypes Leu8-, CD57+, and HLA-DR+, also suggesting activation. These findings indicate that, in HIV infection, the activated CD8 cell subsets that do not survive in medium alone consist of a "normal" component that requires IL2 for survival and an "abnormal" component that does not survive even in IL2.
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PMID:HIV-related alterations in CD8 cell subsets defined by in vitro survival characteristics. 170 1

Murine monoclonal antibodies (mAbs) M38 and L31 define two epitopes of a surface protein of activated lymphocytes and monocytes. It has been shown that M38 also defines a crossreactive epitope of human immunodeficiency virus type 1 (HIV-1) gp120 (Beretta et al., 1987. Eur. J. Immunol. 17: 1793). The mAb inhibits syncytia formation driven by HIV-1-infected cells. The surface protein was demonstrated to be a class I MHC alpha chain, by sequence analysis of the corresponding cDNA and by immunological means. The epitopes defined by mAbs M38 and L31 are monomorphic and hidden (i.e., inaccessible to antibodies) on native HLA molecules expressed by resting cells, but can be evidenced on denatured proteins by Western blot analysis. The two epitopes become accessible after activation processes have been implemented, likely reflecting a conformational alteration of alpha chains (such as that described by Schnabl et al. 1990. J. Exp. Med. 171:1431). Consistent with molecular data are the results of functional analysis, which indicate that the molecule recognized by M38 and L31 is a gate for pleiotropic negative signals, since the two mAbs were shown to inhibit monocyte antigen presentation and lymphocyte mitogenic proliferation, respectively.
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PMID:Human immunodeficiency virus type 1 gp120 mimics a hidden monomorphic epitope borne by class I major histocompatibility complex heavy chains. 171 67

To detect HLA-binding peptides in 10 HIV-1 proteins (Rev, Tat, Vif, Vpr, Vpu, Gag p18, Gag p24, Gag p15, Env gp120 and Env gp41), the peptide binding assay (PBA) has been performed using three HLA class I molecules. Correlations have been searched between the PBA results and the peptide competitor activity in a functional test using HLA-A2-restricted CTL and target cells. A correlation between the data found in the PBA and well-defined CTL epitopes could be attempted only for the three Gag proteins. For these proteins, our results are in agreement with the known existence of epitopes reacting with human CD8+ CTL, with some exceptions. Together with the results reported with a panel of Nef peptides, these experiments showed that at least 18/20 of the already reported CTL epitopes from HIV-1 Gag, Nef, and Env proteins could be detected by the PBA, most (17/18) corresponding to strong reactivities. Perhaps more important, the regions of HIV-1 Gag p24 or Nef proteins that contain multiple associated CTL epitopes, with different HLA restrictions, were clearly identified by the reactivities in the PBA of several overlapping peptides and the major practical interest of the PBA might be the detection of such polyepitopic regions. Prediction are proposed in this report for 10 proteins, including several proteins for which CTL epitopes remain presently unknown.
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PMID:HLA-binding regions of HIV-1 proteins. II. A systematic study of viral proteins. 171 12

In this study, we have investigated by light and electron microscopy the presence, distribution, and inner structure of CD36(OKM5)+ dendritic cells (DC) in the lamina propria and epithelium of the oral mucosa of HIV- and HIV+ subjects; in the latter, both clinically healthy areas and areas of hairy leukoplakia (HL) were studied. Perivascular CD36+ DC were present in the lamina propria of all the specimens studied. They were also found in small numbers in the epithelium of clinically healthy mucosa of HIV- and HIV+ subjects, but were practically absent from the epithelium of HL. CD36+ DC seemed to be regularly HLA-DR+ in HIV-subjects; this positivity was recognized only in some cells in the clinically healthy mucosa of HIV+ subjects, and practically never in HL. Because the only perivascular cells observed in the clinically healthy areas of HIV+ subjects were CD36+, we investigated the ultrastructure of perivascular DC in these same areas. These cells were characterized by the presence of a prominent Golgi apparatus, many lysosomes, and focal adhesions to the extracellular matrix. It may be concluded that 1) CD36+ DC are physiologic components of the oral mucosa, 2) they share some ultrastructural features with macrophages, 3) no differences in numbers were found between HIV+ and HIV- subjects, and 4) these cells are affected in their expression of HLA-DR antigens during HIV infection, particularly in areas of HL. This may be a hint that the antigen-presenting function of these cells in the oral mucosa is negatively affected during HIV infection.
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PMID:CD36(OKM5)+ dendritic cells in the oral mucosa of HIV- and HIV+ subjects. 171 30

A large number of human immunodeficiency virus type 1 (HIV-1) specific HLA-restricted cytotoxic T cell (CTL) epitopes have been mapped, including an HLA-B27-restricted immunodominant epitope within p25gag. Accordingly, this segment of the HIV-1 provirus was amplified by the polymerase chain reaction from DNA derived from fresh uncultured peripheral blood mononuclear cells (PBMC) of four HLA-B27 HIV-1-infected individuals. In all cases the majority of infected PBMC bore sequences encoding the HLA-B27-restricted peptide. CTL escape mutants had not accumulated in vivo 8 and 14 months later despite demonstrable CTL activity in vitro. These data emphasize the importance of silently infected lymphocytes in evading immune surveillance.
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PMID:In vivo persistence of a HIV-1-encoded HLA-B27-restricted cytotoxic T lymphocyte epitope despite specific in vitro reactivity. 171 89

Design of a synthetic vaccine for HIV requires basic knowledge of the structure of helper and cytotoxic T-cell epitopes and neutralizing antibody epitopes, of ways to couple these to produce an effective immunogen, and of the role of viral sequence variation on MHC presentation of antigen. T-cell recognition, and cross-reactivity. We have been addressing all these issues for the HIV envelope and more recently also for the reverse transcriptase. We have now identified antigenic sites or epitopes from HIV envelope and reverse transcriptase recognized by cytotoxic T cells from both mice and humans in association with murine class I H-2 and human class I HLA antigens, as well as epitopes recognized by helper T cells in association with class II MHC molecules from both mice and humans. We have identified residues affecting interaction of peptides with MHC molecules and T-cell receptors and have examined the role of viral variability on presentation of these peptides by MHC molecules and recognition by T cells. One CTL epitope peptide was found to be presented by class II MHC molecules as well as class I MHC molecules and to be able to elicit CD4+ helper cells to aid in the induction of CD8+ CTL against the same peptide. One of the helper epitope peptides has been shown to be a powerful carrier for inducing neutralizing antibodies, and we have shown in rhesus monkeys that some of these helper peptides are immunogenic in primates and can elicit helper T cells that greatly augment the antibody response to a challenge in vivo with a suboptimal dose of HIV envelope protein compared to monkeys not given peptides, as one would want a vaccine to do. We have also identified multideterminant regions of the HIV-1 envelope and have made peptides corresponding to these that elicit helper T-cell responses in a large fraction of mouse strains and of outbred humans, as an approach to overcoming the problem of genetic restriction of T-cell responses. We have also developed a way of using purified recombinant proteins to elicit cytotoxic T cells in vivo by immunizing with the proteins incorporated into ISCOMs, and this method could be applied to an artificial vaccine as well. Some of these peptides should be candidates for immunotherapy trials in HIV-infected humans, as well as for vaccine development and diagnostic use.
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PMID:Progress toward an artificial vaccine for HIV: identification of helper and cytotoxic T-cell epitopes and methods of immunization. 172 61

We studied HLA antigen distribution of 50 heterosexual partners of HIV+ drug abusers with more than 1 year of sexual exposure to HIV, 36 children born to seropositive mothers and 61 haemophiliac patients exposed to presumably infectious clotting factor concentrates. B52 and B44 antigens were associated with HIV resistance while B51 was associated with HIV susceptibility. Forty-nine HIV+ drug abusers, spouses of heterosexual partners studied and 25 HIV+ mothers of the children were also typed. DR11 phenotype was associated with infectiousness of HIV+ subjects. Our data suggest that the HLA region controls susceptibility to infection with HIV and infectiousness of HIV+ subjects in different risk groups.
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PMID:HLA-associated susceptibility to HIV-1 infection. 173 33


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