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

Human immunodeficiency virus type 1 (HIV-1)-infected persons frequently have increased numbers of T cells bearing the gamma delta T cell receptor for antigen (gamma delta TCR). HIV-1-seropositive patients with < 100 CD4+ cells/mm3 were selected and divided into 9 AIDS-defining illness groups. The percentages of CD4+, CD8+, or double-negative CD4-CD8- (DN) T cells (most of the latter expressing the gamma delta TCR) for 8 symptomatic groups were compared with those for a reference group of asymptomatic HIV-1-infected patients. DN T cells were increased only in patients with disseminated Mycobacterium avium-intracellulare complex (MAC) infection, toxoplasmosis, or Kaposi's sarcoma. Multivariate logistic regression analysis revealed that the percentage of DN T cells was a better predictor of MAC infection than was the percentage of CD4+T cells. The increased percentage of DN T cells might have important implications for the understanding of gamma delta T cell physiology and for the early diagnosis and management of MAC infections in AIDS patients.
 ...
PMID:Increases in CD3+CD4-CD8- T lymphocytes in AIDS patients with disseminated Mycobacterium avium-intracellulare complex infection. 889 97

T helper (Th) epitopes can be included in a recombinant protein with B and CTL epitopes to create more effective immunogens. To determine whether the antigenicity of HIV Th epitopes is preserved in this altered molecular context, human Th clones specific for peptides of HIV gp120 and reverse transcriptase p66 were challenged with recombinant proteins carrying the antigenic epitopes in different sites. We found that a given epitope was recognized by a specific T cell clone only when it was inserted in a particular position of the carrier. However, the permissive position was not the same for all epitopes. Enzymatic excision from a nonpermissive context or insertion of a polyserine spacer between the epitope and the carrier restored antigenicity. Nevertheless, antigenicity was not abolished in a synthetic peptide encompassing the epitope and the neighboring residues from the nonpermissive location. These data suggest that, in this case, the primary sequence of the chimeric protein flanking the HIV peptide is not responsible for loss of antigenicity. Furthermore, constructs carrying the epitope in a given position were recognized by peptide-specific Th clones raised from some individuals, but not from others. We show that this is due neither to individual modes of processing nor to the use of distinct major histocompatibility complex MHC class II restriction elements, but rather that it is related to the fine specificity of the clones. To study the effect of epitope context on selection of T cell repertoire in a naive individual, T cell lines were generated in vitro by stimulation with different peptide constructs. This resulted in the induction of diverse clonotypes defined by the pattern of recognition of different constructs, by T cell receptor V beta gene usage and by fine epitope mapping.
 ...
PMID:Antigenicity of HIV-derived T helper determinants in the context of carrier recombinant proteins: effect on T helper cell repertoire selection. 889 61

Perturbations of the repertoire of variable-beta (Vbeta) regions of the T cell receptor have been observed in patients infected by HIV and have been attributed to stimulation by viral antigens or superantigens. We further sought for traces of HIV-induced perturbations by comparing Vbeta repertoire in peripheral blood and in lymphoid tissues of six infected patients. Vbeta expression was studied with a panel of 17 anti-Vbeta antibodies covering about 50% of the entire repertoire. We observed major divergences between lymph nodes and peripheral blood in the expression of several Vbeta segments, and these differences were significantly more frequent in CD8+ than in CD4+ T cells (P = 0.0097). Vbeta2 was perturbed in CD8 cells from all but one patient. One HIV-negative subject with localized reactive lymphadenopathy of unknown etiology had four perturbed Vbeta segments, including Vbeta2, in CD8+ cells, while another uninfected subject with an unreactive lymph node architecture had no perturbations. Our findings suggest that stimulation by HIV or by other antigens determines divergences in the Vbeta repertoire between lymphoid tissues and peripheral blood predominantly in CD8+ T cells.
 ...
PMID:Comparison of the Vbeta repertoire in peripheral blood and in lymph nodes of HIV-infected subjects reveals skewed usage predominantly in CD8+ T cells. 890 52

Late-stage HIV-1 disease in humans has been associated with perturbations of the T cell receptor (TCR) Vbeta repertoire. It is not known if the observed loss of certain Vbeta families is attributable directly to HIV-1 infection or whether this is a consequence of multiple opportunistic infections. Putative HIV-1-associated superantigens have been postulated to be the cause of the perturbed TCR Vbeta repertoire and the subsequent CD4+ T cell depletion in HIV-1-infected humans. In this study, we examined the human TCR Vbeta repertoire in SCID-hu mice, housed in a pathogen-free environment and infected with a molecularly cloned virus strain, to ascertain directly the effect of HIV-1 on the human TCR Vbeta repertoire in the absence of other infectious agents. We demonstrate that mock-infected human thymus/liver (Thy/Liv) implants in SCID-hu mice have complete TCR Vbeta repertoires, reflective of a normal human thymus. However, HIV-1-infected implants in SCID-hu mice had depleted TCR Vbeta repertoires, corresponding with thymocyte depletion. These results indicate that HIV-1-specific mechanisms are the cause of the TCR Vbeta repertoire depletion in infected implants. However, these thymocyte depletions were not restricted to specific TCR Vbeta subsets. These results are not consistent with the hypothesis that HIV-1 acts as a superantigen in vivo. The disruption of the TCR Vbeta repertoire in the human Thy/Liv implants of the SCID-hu mice suggests that HIV-1 infection may be influencing T cell development in the thymus, contributing to both the overall CD4+ T cell depletion in AIDS and limited TCR repertoire diversity.
 ...
PMID:Loss of T cell receptor Vbeta repertoires in HIV type 1-infected SCID-hu mice. 900 98

Sporadic inclusion body myositis (IBM) is the most common inflammatory myopathy affecting patients over the age of 50 years. Dysimmune and degenerative aetiologies have been postulated, but viral infections have not been associated with the disease. Two HIV-I (human immunodeficiency virus type 1) infected men and one woman infected with HTLV-1 (human T cell leukaemia virus type 1) developed progressive proximal muscle weakness unrelated to antiretroviral therapy. Their muscle biopsies were studied by light and electron microscopy, by immunocytochemistry to determine the expression of major histocompatibility complex (MHC) molecules and identify the type of infiltrating cells and T cell receptor (TCR) subunits, and by reverse transcription-polymerase chain reaction (RT-PCR) and single or double immunocytochemistry to search for retrovirally infected endomysial cells. The clinical features were consistent with sporadic IBM. The muscle biopsies showed primary endomysial inflammation, red-rimmed vacuoles, amyloid deposits, eosinophilic inclusions, and small round fibres in groups, all diagnostic of IBM. The muscle fibres expressed MHC class-1 antigens and were invaded primarily by CD8+ T-lymphocytes preferentially bearing TCR V beta 5.1 and V beta 13 chains. The HIV-1 or HTLV-1 antigens were detected only on endomysial macrophages on or around muscle fibres, but not within the muscle fibres. We conclude that IBM occurs in HIV-1 and HTLV-1 infected individuals and has a clinical, histological and immunological pattern identical to sporadic IBM in the non-retrovirally infected patients. Retroviruses do not directly infect the muscle, but persistent retroviral infections may provide superantigenic stimulation and trigger an endomysial inflammatory response identical to that occurring in sporadic IBM.
 ...
PMID:Inclusion body myositis in HIV-1 and HTLV-1 infected patients. 900 95

We have expressed in bacteria a single-chain T cell receptor (scTCR) with specificity for an HIV gp120-derived peptide bound to the murine MHC-I molecule, H-2Dd. This scTCR consists of V alpha covalently linked to the VbetaCbeta domains that was solubilized, refolded, and purified in high yield. Specific binding of the scTCR to MHC/peptide complexes was demonstrated by surface plasmon resonance, with a Kd of 2 to 8 x 10(-6) M. This scTCR specifically inhibited T cell activation, and stained cell surface MHC/peptide complexes as measured by cytofluorimetry. The preservation of binding specificity by such a three-domain scTCR suggests that this structure is sufficient for specific MHC/peptide recognition and that this strategy will be of general use as applied to other TCR.
 ...
PMID:A three-domain T cell receptor is biologically active and specifically stains cell surface MHC/peptide complexes. 903 68

The Nef protein alters T cell receptor (TCR) signaling in T cells and is critical for the pathogenesis of AIDS. We used a transient expression assay in a human CD4+ T cell line to analyze the interaction of Nef with the TCR machinery. We show that, in addition to down-regulating CD4 expression on the cell surface, Nef blocks a receptor-proximal event in CD3 signaling. Analysis of a large number of mutant Nef proteins demonstrated that the effects of Nef on CD4 expression and on CD3 signaling are separable. The ability of Nef to block CD3 signaling was selectively abolished by mutations in the central part of the Nef protein and in particular by those known to disrupt the SH3 binding surface in the structured core of Nef. In contrast, the ability of Nef to down-regulate CD4 expression was selectively abolished by two clusters of mutations, one in the N-terminal and one in the C-terminal region of Nef. These two regions correspond to the two flexible loops in Nef as predicted by solution NMR analysis. We show that this general functional organization is conserved between the Nef proteins of the human and simian immunodeficiency viruses (HIV-1 and SIV). Our data demonstrate that Nef has at least two independent mechanisms to alter TCR function and thus may interfere with a range of T cell responses.
 ...
PMID:Separable functions of Nef disrupt two aspects of T cell receptor machinery: CD4 expression and CD3 signaling. 904 97

The product of the dek oncogene is the 43-kDa DEK nuclear protein. DEK was first identified in a fusion with the CAN nucleoporin protein in a specific subtype of acute myelogenous leukemia. DEK has also been shown to be an autoantigen in patients with pauciarticular onset juvenile rheumatoid arthritis. Further, the last 65 amino acids of DEK can partially reverse the mutation-prone phenotype of cells from patients with ataxia-telangiectasia. However, in spite of these significant disease associations, the function of DEK has remained unclear. The HIV-2 peri-ets (pets) site is a TG-rich element found between the two Elf-1 binding sites in the HIV-2 enhancer. The pets element mediates transcriptional activation whether the enhancer is stimulated by phorbol 12-myristate 13-acetate (PMA) alone, phytohemagluttinin (PHA) alone, PMA plus PHA, soluble antibodies to the T cell receptor, immobilized antibodies to the T cell receptor, or by antigen. Previously, we purified and characterized the pets factor, demonstrating that it is a 43-kDa nuclear protein. We now describe the identification of DEK as this 43-kDa pets factor. Using a modified Southwestern screening procedure, we find that DEK can recognize the pets element. We demonstrate the ability of recombinant DEK to bind specifically to the pets site using the electrophoretic mobility shift assay (EMSA) and DNase I footprinting. "Supershift" EMSA further confirms that DEK is the dominant protein binding to the pets site in T cell extracts. Our findings show that DEK is a site-specific DNA binding protein that is likely involved in transcriptional regulation and signal transduction. This has implications for multiple pathogenic processes, including hematologic malignancies, arthritis, ataxia-telangiectasia, and AIDS caused by HIV-2.
 ...
PMID:DEK, an autoantigen involved in a chromosomal translocation in acute myelogenous leukemia, binds to the HIV-2 enhancer. 905 Aug 61

B7 co-stimulation is essential for activating resting T cells following antigen recognition by the T cell receptor. To determine whether B7 has adjuvant activities on human immunodeficiency virus type-1 (HIV-1)-specific immunity induced by inoculation of a plasmid encoding HIV-1 env and rev (DNA vaccine), B7-1 and B7-2 expression plasmids were co-inoculated with the DNA vaccine. The delayed-type hypersensitivity response and cytotoxic T lymphocyte (CTL) activity were significantly enhanced when B7-2 expression plasmid was co-inoculated with the DNA vaccine, but were unaffected when the B7-1 expression plasmid was used with the vaccine instead. The immunological response enhanced by B7-2 decreased below the level of mice immunized with the DNA vaccine in combination with CTLA4Ig, an inhibitor of the B7/CD28 co-stimulatory signal, suggesting that this signal is critical for the enhanced response induced by co-inoculation of the DNA vaccine and B7-2 expression plasmid. This enhancement appeared to occur via an interferon-gamma (IFN-gamma)-dependent mechanism, as combined administration of the B7-2 plasmid and neutralizing anti-IFN-gamma antibody abrogated the virus-specific cell-mediated immunity. These results suggest that this gene-based co-inoculation strategy using HIV-1 viral antigen and B7-2 co-stimulatory molecule could be a powerful means of combating HIV-1 infection.
 ...
PMID:Immunomodulatory effects of a plasmid expressing B7-2 on human immunodeficiency virus-1-specific cell-mediated immunity induced by a plasmid encoding the viral antigen. 907 22

To address the possible role of replicative senescence in human immunodeficiency virus (HIV) infection, telomere length, telomerase activity, and in vitro replicative capacity were assessed in peripheral blood T cells from HIV+ and HIV- donors. Genetic and age-specific effects on these parameters were controlled by studying HIV-discordant pairs of monozygotic twins. Telomere terminal restriction fragment (TRF) lengths from CD4+ T cells of HIV+ donors were significantly greater than those from HIV- twins. In contrast, telomere lengths in CD8+ T cells from HIV+ donors were shorter than in HIV- donors. The in vitro replicative capacity of CD4+ cells from HIV+ donors was equivalent to that of HIV- donors in response to stimulation through T cell receptor CD3 and CD28. Little or no telomerase activity was detected in freshly isolated CD4+ or CD8+ lymphocytes from HIV+ or HIV- donors, but was induced by in vitro stimulation of both HIV+ and HIV- donor cells. These results suggest that HIV infection is associated with alterations in the population dynamics of both CD4+ and CD8+ T cells, but fail to provide evidence for clonal exhaustion or replicative senescence as a mechanism underlying the decline in CD4+ T cells of HIV-infected donors.
 ...
PMID:Telomere length, telomerase activity, and replicative potential in HIV infection: analysis of CD4+ and CD8+ T cells from HIV-discordant monozygotic twins. 910 24


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>