Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0021051 (immunodeficiency)
 71,517 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have recently reported the isolation of a human immunodeficiency virus type 1 (HIV-1), KB-1gp32 carrying a shorter size (32 kDa) of transmembrane glycoprotein (TMP) from TALL-1 cells persistently infected with KB-1gp41 virus strain (Shimizu et al., 1990a). Endoglycosidase treatments showed that the different size of the TMP between the two strains was due to a truncation of 9 kDa of polypeptide in the KB-1gp32 TMP coding region. Sequence analysis revealed the substitution of a CAG codon to a TAG stop codon just downstream of the putative membrane-spanning domain of the TMP of KB-1gp32. This resulted in a truncation of some 133 amino acids of the cytoplasmic domain of TMP. The data indicate that a premature stop codon in KB-1gp32 has been introduced during adaption of the parental virus to TALL-1 cells. We have constructed two chimeric clones between the env region of a clone pKB-1, derived from KB-1gp32, and an infectious molecular clone pNL-432. We have also constructed a site-directed mutant of pNL-432 carrying a premature stop codon at the same position as the env stop codon of pKB-1. Among the three clones carrying a premature stop codon in env, only one chimeric clone was infectious to TALL-1 but not MT-2 cells. This clone contained the entire tat, rev, vpu, and env genes of pKB-1. The pNL-432 mutant was not infectious. The results suggest that some sequences of pKB-1 might compensate for the truncation of the TMP during replication in TALL-1 cells.
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PMID:Analysis of a human immunodeficiency virus type 1 isolate carrying a truncated transmembrane glycoprotein. 132 87

We have previously shown that immunization with solid matrix-antigen-antibody (SMAA) complexes induces both vigorous humoral and cell-mediated immune responses and have suggested that this method of vaccination may be developed for use in humans, and potentially as a vaccine against AIDS. Here we demonstrate that a small oligopeptide can act as a tag for the construction of SMAA complexes using a tag-specific monoclonal antibody and tag-linked antigens. We show that a 14-amino acid oligopeptide, present in the phospho (P) and V proteins of simian virus 5 (SV5), retains its antigenicity when attached to the C terminus of three 'foreign' proteins [p27 and gp110 of simian immunodeficiency virus (SIV) and glutathione S-transferase] such that these proteins can be incorporated into SMAA complexes using a monoclonal antibody (MAb) that was originally raised against the native SV5 P and V proteins. Mice were immunized with SMAA complexes containing recombinant p27-TAG and MAbs have been isolated that recognized native SIV p27. The significance of these results in terms of the development of SMAA complexes as human vaccines is discussed.
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PMID:Construction of solid matrix-antibody-antigen complexes containing simian immunodeficiency virus p27 using tag-specific monoclonal antibody and tag-linked antigen. 137 38

NF-kappa B is a DNA-binding regulatory factor able to control transcription of a number of genes, including human immunodeficiency virus (HIV) genes. In T cells, NF-kappa B is activated upon cellular treatment by phorbol esters and the cytokine tumor necrosis factor alpha (TNF alpha). In the present work, we investigated the molecular events leading to NF-kappa B activation by TNF alpha in a human T cell line (Jurkat) and its subclone JCT6, which presents a deficiency in the PKA transduction pathway. We found that in both cell lines, both phorbol ester and TNF alpha were able to activate NF-kappa B. Phorbol activation was positively modulated by Ca2+ influx while TNF alpha activation was not. Furthermore, while PMA activation was inhibited by the PKC inhibitor staurosporin, the TNF alpha effect was unchanged. TNF alpha did not activate cAMP production and its signal was not modulated by cAMP activators. Moreover, cAMP activators did not activate NF-kappa B in Jurkat cells. Thus, TNF alpha-induced NF-kappa B activation was found to be mediated by none of the major signal-mediating kinases such as protein kinase C (PKC), protein kinase A, or Ca(2+)-regulated kinases. Furthermore, we found that cytoplasmic acidification facilitated NF-kappa B activation by both TNF alpha and PKC, by a mechanism that increases NF-kappa B/I kappa B dissociation without affecting the NF-kappa B translocation step.
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PMID:NF-kappa B activation by tumor necrosis factor alpha in the Jurkat T cell line is independent of protein kinase A, protein kinase C, and Ca(2+)-regulated kinases. 165 56

Transcriptional regulation of the proviral form of the human immunodeficiency virus type 1 (HIV-1) is exerted by its 5' long terminal repeat (LTR), which contains recognition sites for several cell factors. By gel retardation and DNase I footprinting experiments we have identified a binding site for a human nuclear protein between nucleotides -152 to -174 upstream of transcription start site, in a region previously recognized as a negative regulator of transcription (negative regulatory element, NRE). The recognized sequence contains the dyad symmetry element CACGTG, which represents a binding motif, very conserved through evolution, present in a putative human DNA replication origin (pB48), in the upstream element of the major late promoter (MLP-UE) of adenovirus, and, as transcriptional element, upstream of many eukaryotic genes. Common binding activities exist in human nuclear extracts for pB48, MLP-UE and the HIV-1 LTR; at least three protein species recognize the LTR sequence, of 44 (corresponding to transcription factor USF/MLTF), 70, and 110 kDa, respectively. Chloramphenicol acetyltransferase assays suggest that the USF/MLTF binding site located in the HIV-1 LTR acts as a negative regulator of transcription, and that it contributes to the overall negative function exerted by the NRE. An oligonucleotide corresponding to another characterized human USF/MLTF binding site can functionally replace part of the activity of the NRE. This negative function is exerted both in presence or absence of tat transactivation, in different cell lines, and after PMA stimulation.
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PMID:A human binding site for transcription factor USF/MLTF mimics the negative regulatory element of human immunodeficiency virus type 1. 172 95

Three lines of transgenic mice carrying the human immunodeficiency virus type 1 (HIV-1) long terminal repeat fused to the simian virus 40 early region (HIV-1 Tag) were constructed. Expression of the transgenes was reproducibly observed in the lymphoid tissue and skin of all three transgenic lines studied. Interestingly, cell types other than T cells, i.e., B cells and thymic stromal cells, contributed most of the expression detectable in the lymphoid organs. Each transgenic line also displayed a different but consistent pattern of transgene expression in nonlymphoid organs. These individual patterns probably reflect the effects of particular chromosomal integration sites on transcriptional activity of the HIV-1 promoter.
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PMID:Expression of a human immunodeficiency virus type 1 long terminal repeat/simian virus 40 early region fusion gene in transgenic mice. 184 96

Activation of T lymphocytes infected with the human immunodeficiency virus-1 (HIV-1) results in enhancement of viral replication mediated in part by activation of cellular NF kappa B capable of binding directly to sequences in the viral long terminal repeat, or LTR. Together with CD4+ T cells, macrophages constitute a major target for infection by HIV-1. Unlike lymphocytes, however, stimulation of mononuclear phagocytes is not associated with cell division and proliferation. Human monocyte-derived macrophages transfected with HIV-LTR-CAT constructs demonstrated down-regulation of CAT activity after stimulation with bacterial lipopolysaccharide (LPS) that mapped to a region distinct from NF kappa B binding sites. In contrast, fresh monocytes and the promonocytic U937 cell line both demonstrated up-regulation of HIV-LTR-CAT expression by LPS. Differentiation of U937 by PMA to establish a nondividing phenotype resulted in down-regulation of transfected HIV-LTR-CAT activity by LPS similar to that in mature macrophages. Human monocyte-derived macrophages infected with HIV-1 in vitro demonstrated a decrease in viral p24 release after incubation in LPS that was comparable to the negative regulation that occurred in the transient transfection assays. Factors controlling HIV replication may differ in dividing and nondividing hematopoietic cells and may contribute to restricted viral expression in nondividing cells.
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PMID:Activation of human monocyte--derived macrophages with lipopolysaccharide decreases human immunodeficiency virus replication in vitro at the level of gene expression. 190 15

The production of human immunodeficiency virus type 1 (HIV-1) progeny was followed in the U937 promonocytic cell line after stimulation either with retinoic acid or PMA, and in purified human monocytes and macrophages. Electrophoretic mobility shift assays and Southwestern blotting experiments were used to detect the binding of cellular transactivation factor NF-KB to the double repeat-KB enhancer sequence located in the long terminal repeat. PMA treatment, and not retinoic acid treatment of the U937 cells acts in inducing NF-KB expression in the nuclei. In nuclear extracts from monocytes or macrophages, induction of NF-KB occurred only if the cells were previously infected with HIV-1. When U937 cells were infected with HIV-1, no induction of NF-KB factor was detected, whereas high level of progeny virions was produced, suggesting that this factor was not required for viral replication. These results indicate that in monocytic cell lineage, HIV-1 could mimic some differentiation/activation stimuli allowing nuclear NF-KB expression.
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PMID:Induction of NF-KB during monocyte differentiation by HIV type 1 infection. 198 49

T cell lines with a novel phenotype (CD3+ TCR-alpha/beta+ CD4- CD8-) were developed from the peripheral blood of a patient with a combined immunodeficiency and tissue injury resembling graft-vs-host disease. One of these IL-2-dependent T cell lines demonstrated non-MHC-restricted cytolytic function against tumor targets, syngeneic and allogeneic fibroblasts, and PHA blasts from allogeneic donors. The other cell line only became cytotoxic in the presence of lectin or anti-CD3 antibody. The two cell lines also differed in their expression of the T-200 gene products CD45RO (gp180) and CD45RA (gp220). Both cell lines produced tumor necrosis factor-alpha and -beta and IFN-gamma activity when activated with mitogens or PMA and IL-1. The in vitro functions of these T-cell lines suggest a potential role for alpha/beta double-negative T lymphocytes in tissue injury resembling graft-vs-host disease.
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PMID:Double-negative (CD4- CD8-) T cells with an alpha/beta T cell receptor. Non-MHC-restricted cytolytic activity and lymphokine production. 214 Oct 37

Human immunodeficiency virus (HIV) spends a significant part of the viral life cycle as a latent provirus integrated into the host genome. Activation of latent HIV-1 requires mitogenic stimulation of the cell, which increases basal viral transcription, and the HIV-1 tat protein. As tat itself dramatically increases HIV-1 gene expression, it too is presumably regulated in the latent state, and may also be activated by mitogenic stimulation. We show here that depletion of protein kinase C (PKC), which is essential to the stimulation of T cells by several mitogens, dramatically reduces HIV-1 transactivation without affecting synthesis of tat protein. Transactivation in PKC-depleted cells can be restored by transfection with a PKC expression vector. The requirement for PKC in trans-activation does not involve the PMA-responsive enhancer elements responsible for the effect of mitogens on basal transcription. Our results indicate that PKC regulates the process of HIV-1 transactivation, suggesting a key role for the mitogenic induction of trans-activation in the transition of HIV from latency to productive growth.
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PMID:Trans-activation of HIV-1 LTR-directed gene expression by tat requires protein kinase C. 218 21

Functional studies were performed on human peripheral blood T lymphocytes stained with goat anti-5'-nucleotidase antibodies and separated into ecto-5'-nucleotidase (ecto-5'-NT)-positive and -negative populations using the FACSTAR fluorescence-activated cell sorter. On the average, ecto-5'-NT+ T cells contained 34 +/- 13% CD4+ and 55 +/- 15% CD8+ cells, whereas ecto-5'-NT-T cells contained 65 +/- 12% CD4+ and 23 +/- 8% CD8+ cells. Staining with anti-5'-NT antibodies did not significantly alter the ability of unseparated T cells to proliferate in response to PHA or PMA, or in a MLR. However, prior incubation with anti-5'-NT antibodies did inhibit the ability of irradiated T cells to provide help for PWM-stimulated Ig synthesis by as much as 55%. In five separate experiments, ecto-5'-NT-T cells demonstrated an equal or better ability to incorporate [3H]TdR after PHA stimulation or in a MLR, as compared with ecto-5'-NT+ T cells. Similarly, ecto-5'-NT- T cells were not diminished in their ability to provide help for autologous B cells in a PWM-driven system. Clearly, the inability of ecto-5'-NT- T cells from patients with a variety of immunodeficiency diseases to function in these assays cannot be explained solely by their lack of ecto-5'-NT activity. In contrast, ecto-5'-NT-positive and -negative T cells showed markedly different dose-response curves for proliferation in response to PMA. Ecto-5'-NT+ T cells responded to lower doses of PMA (1.0 ng/ml) than did ecto-5'-NT- T cells and showed a two- to eight-fold greater rate of [3H]TdR incorporation at 3 to 10 ng of PMA per ml. Ecto-5'-NT+ T cells may have a protein kinase C that is more accessible or more easily activated or may utilize an alternate pathway of activation when stimulated with low concentrations of PMA.
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PMID:Functional characterization of ecto-5'-nucleotidase-positive and -negative human T lymphocytes. 253 56


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