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)

The mechanism of trans-acting regulation of transcription from the long terminal repeat (LTR) of human immunodeficiency virus (HIV) has been investigated. The roles of the cis-acting elements within HIV LTR, as well as the trans-acting factors present in HIV-infected cells, have been evaluated by an in vitro transcription system. Our observations indicate that both the sequence downstream from the CAP site of HIV LTR (located at nucleotide positions +1 to +56; called the TAR element) and the GC boxes (-77 to -45) are required for full transcriptional stimulation and that both the virus-encoded tat protein and one or more cellular factors might be involved. These results demonstrate the presence of a combinatorial regulation of HIV transcription by multiple factors, which may confer the provirus with greater flexibility in regulated viral gene expression.
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PMID:Transcriptional activation from the long-terminal repeat of human immunodeficiency virus in vitro. 237 70

Alterations of sleep structure have been reported in asymptomatic human immunodeficiency virus (HIV)-infected subjects. In these patients some authors have found an increased percentage of slow wave sleep (SWS) and a SWS preponderance in the second half of the night, as well as subjective sleep complaints. Other authors have found an increased stage 1 non-rapid eye movement (NREM) and reduced stage 2 NREM percentages in asymptomatic subjects. We evaluated the macrostructure and the microstructure (cyclic alternating pattern, CAP) of sleep in nine HIV-infected asymptomatic men without sleep complaints or psychiatric illness, in comparison with nine age-matched controls. Our study showed a decreased amount of SWS and a significantly higher CAP rate in HIV-subjects, suggesting an altered organization of the sleep process in these patients.
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PMID:Slow wave sleep and cyclic alternating pattern (CAP) in HIV-infected asymptomatic men. 748 16

Current clinical gene therapy protocols for the treatment of human immunodeficiency virus type 1 (HIV-1) infection often involve the ex vivo transduction and expansion of CD4+ T cells derived from HIV-positive patients at a late stage in their disease (CD4 count <400). These protocols involve the transduction of T cells by murine leukemia virus (MLV)-based vectors encoding antiviral constructs such as the rev m10 dominant negative mutant or a ribozyme directed against the CAP site of HIV-1 RNA. We examined the efficiency and stability of transduction of CD4+ T cells derived from HIV-infected patients at different stages in the progression of their disease, from seroconversion to AIDS. CD4+ T cells from HIV-positive patients and uninfected donors were transduced with MLV-based vectors encoding beta-galactosidase and an intracellular antibody directed against gp120 (sFv 105) or Tat. (sFvtat1-Ckappa). The expression of marker genes and the effects of the antiviral constructs were monitored in vitro in unselected transduced CD4+ T cells. Efficiency and stability of transduction varied during the course of HIV infection; CD4+ T cells derived from asymptomatic patients were transducible at higher efficiencies and stabilities than CD4+ T cells from patients with acquired immunodeficiency syndrome (AIDS). Expression of the anti-tat intracellular antibody was more effective at stably inhibiting HIV-1 replication in transduced cells from HIV-infected individuals than was sFv 105. The results of this study have important implications for the development of a clinically relevant gene therapy for the treatment of HIV-1 infection.
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PMID:Inhibition of human immunodeficiency virus replication and growth advantage of CD4+ T cells from HIV-infected individuals that express intracellular antibodies against HIV-1 gp120 or Tat. 952 10

CD8(+) lymphocytes from human immunodeficiency virus (HIV)-infected patients can suppress in vitro HIV replication in CD4(+) T cells by a noncytolytic mechanism involving secreted CD8(+)-cell antiviral factor(s) (CAF). Using an HIV Nef-specific cytotoxic-T-lymphocyte (CTL) line and autologous CD4(+) T cells infected with a nef-deleted HIV-1 virus, we demonstrated that, after a priming antigenic stimulation, this suppression does not require the presence of the specific antigen during the effector phase. Furthermore, using an Epstein-Barr virus (EBV)-specific CTL line from an HIV-seronegative donor, we demonstrated that the ability to inhibit HIV replication in a noncytolytic manner is not restricted to HIV-specific effector cells; indeed, EBV-specific CTL were as efficient as HIV-specific effectors in suppressing R5 or X4 HIV-1 strain replication in vitro. This HIV-suppressive activity mediated by a soluble factor(s) present in the culture supernatant was detectable for up to 14 days following stimulation of EBV-specific CD8(+) cells with the cognate epitope peptide. Following acute infection of CEM cells with an X4 strain of HIV-1, EBV-specific CTL line supernatant containing HIV-suppressive activity did not block virus entry but was shown to interfere with virus replication after the first template switching of reverse transcription. Our results suggest that the noncytolytic control of HIV replication by EBV-specific CD8(+) T lymphocytes corresponded to a CAF-like activity and thus demonstrate that CAF production may not be restricted to CTL induced during HIV disease. Moreover, CAF acts after reverse transcription at least for X4 isolate replication inhibition.
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PMID:CD8(+)-Cell antiviral factor activity is not restricted to human immunodeficiency virus (HIV)-specific T cells and can block HIV replication after initiation of reverse transcription. 1077 81

CD8(+) T lymphocytes can suppress human immunodeficiency virus type 1 (HIV-1) replication by secreting a soluble factor(s) known as CD8(+) T-lymphocyte antiviral factor (CAF). One site of CAF action is inhibition of HIV-1 RNA transcription, particularly at the step of long terminal repeat (LTR)-driven gene expression. However, the mechanism by which CAF inhibits LTR activation is not understood. Here, we show that conditioned media from several herpesvirus saimari-transformed CD8(+) T lymphocytes inhibit, in a time- and dose-dependent manner, the replication of HIV-1 pseudotype viruses that express the envelope glycoproteins of vesicular stomatitis virus (HIV-1(VSV)). The same conditioned media also inhibit phorbol myristate acetate-induced activation of the HIV-1 LTR and activate the signal transducer and activator of transcription 1 (STAT1) protein. We have obtained direct evidence that STAT1 is necessary for CAF-mediated inhibition of LTR activation and HIV-1 replication. Thus, the inhibitory effect of CAF on HIV-1(VSV) replication was abolished in STAT1-deficient cells. Moreover, CAF inhibition of LTR activation was diminished both in STAT1-deficient cells and in cells expressing a STAT1 dominant negative mutant but was restored when STAT1 was reintroduced into the STAT1-deficient cells. We also observed that CAF induced the expression of interferon regulatory factor 1 (IRF-1), and that IRF-1 gene induction was STAT-1 dependent. Taken together, our results suggest that CAF activates STAT1, leading to IRF-1 induction and inhibition of gene expression regulated by the HIV-1 LTR. This study therefore helps clarify one molecular mechanism of host defense against HIV-1.
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PMID:A soluble factor(s) secreted from CD8(+) T lymphocytes inhibits human immunodeficiency virus type 1 replication through STAT1 activation. 1175 48

CD8(+) T-cells secrete soluble factor(s) capable of inhibiting both R5- and X4-tropic strains of human immunodeficiency virus type 1 (HIV-1). CCR5 chemokine ligands, released from activated CD8(+) T-cells, contribute to the antiviral activity of these cells. These CC-chemokines, however, do not account for all CD8(+) T-cell antiviral factor(s) (CAF) released from these cells, particularly because the elusive CAF can inhibit the replication of X4 HIV-1 strains that use CXCR4 and not CCR5 as a coreceptor. Here we demonstrate that activated CD8(+) T-cells of HIV-1-seropositive individuals modify serum bovine antithrombin III into an HIV-1 inhibitory factor capable of suppressing the replication of X4 HIV-1. These data indicate that antithrombin III may play a role in the progression of HIV-1 disease.
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PMID:Purification of a modified form of bovine antithrombin III as an HIV-1 CD8+ T-cell antiviral factor. 1219 9

The accessory Vpr protein of human immunodeficiency virus type 1 (HIV-1) is a promiscuous activator of viral and cellular promoters. We report that Vpr enhances expression of the glucocorticoid receptor-induced mouse mammary tumor virus (MMTV) promoter and of the Tat-induced HIV-1 long terminal repeat promoter by directly binding to p300/CBP coactivators. In contrast, Vpr does not bind to p/CAF or to members of the p160 family of nuclear receptor coactivators, such as steroid receptor coactivator 1a and glucocorticoid receptor (GR)-interacting protein 1. Vpr forms a stable complex with p300 and also interacts with the ligand-bound glucocorticoid receptor in vivo. Mutation analysis showed that the C-terminal part of Vpr binds to the C-terminal portion of p300/CBP within amino acids 2045 to 2191. The same p300 region interacts with the p160 coactivators and with the adenovirus E1A protein. Accordingly, E1A competed for binding to p300 in vitro. Coexpression of E1A or of small fragments of p300 containing the Vpr binding site resulted in inhibition of Vpr's transcriptional effects. The C-terminal part of p300 containing the transactivating region is required for Vpr transactivation, whereas the histone acetyltransferase enzymatic region is dispensable. Vpr mutants that bind p300 but not the GR did not activate expression of the MMTV promoter and had dominant-negative effects. These results indicate that Vpr activates transcription by acting as an adapter linking transcription components and coactivators.
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PMID:Human immunodeficiency virus type 1 (HIV-1) accessory protein Vpr induces transcription of the HIV-1 and glucocorticoid-responsive promoters by binding directly to p300/CBP coactivators. 1220 51

In this preliminary study, we evaluated the performance of the Cobas AmpliPrep/Cobas Amplicor HIV-1 Monitor Ultrasensitive Test (CAP; Roche Molecular Systems, Branchburg, NJ) for automated specimen preparation and quantitative detection of human immunodeficiency virus type 1 (HIV-1) RNA and compared it to the Cobas Amplicor HIV-1 Monitor Ultrasensitive Test (MCA; Roche), which includes a manual sample preparation protocol. A dilution panel of a patient sample was prepared. Additionally, 584 EDTA plasma samples were collected from HIV-1 infected patients. Reproducibility was estimated with six assay runs using the dilution panel. The inter-assay coefficient of variation ranged from 39.4 to 48.4% (CAP assay) and from 34.3 to 45.6% (MCA assay), whereas the intra-assay coefficient of variation ranged from 6.2 to 58.0% (CAP assay) and from 4.4 to 57.3% (MCA assay). Comparison of CAP assay results with the HIV-1 copy number of the dilution panel determined by the MCA assay resulted in a good agreement, although the CAP results were found to be slightly lower. A significant correlation between both test systems was found when clinical samples were analyzed. The mean viral load of 152 samples, which were within the linear range of both tests, was 3.70 log(10) HIV-1 copies/ml by the CAP assay compared to 3.73 by the MCA assay. In conclusion, we could demonstrate that the new Cobas AmpliPrep/Cobas Amplicor HIV Monitor Ultrasensitive Test is reproducible and sensitive. In comparison to the assay with manual extraction, no significant difference in HIV-1 RNA copy numbers was observed.
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PMID:Evaluation of the Cobas AmpliPrep/Cobas Amplicor HIV-1 Monitor Ultrasensitive Test: comparison with the Cobas Amplicor HIV-1 Monitor test (manual specimen preparation). 1246 84

Interleukin-2 (IL-2) is a cytokine produced by lymphocytes T CD4+, T CD8+ and NK cells. IL-2 increases the number of lymphocytes T and prolongs their survival and has extensive immunomodulatory effect. High levels of IL-2 are observed during asymptomatic phase of HIV infection (TH-1 dependent cytokine) and low levels are observed during progression of immunodeficiency. IL-2 inhibits apoptosis of CD4+ T cells, improves NK cells activity, has influence on production of soluble antiviral factor (CAF) which inhibits viral activity etc. That is why IL-2 has been introduced to the treatment of HIV infection along with highly active antiretroviral therapy (HAART). High T CD4+ cells count predicts long survival of HIV infected individual. Phase III clinical trials concerning IL-2 are now performed and the preliminary results are promising. Polish centers also take part in the ESPRIT study. Adverse events of various severity are seen in patients under treatment (anti inflammatory drugs are required). The symptoms usually resolve within a few days after IL-2 therapy is stopped.
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PMID:[The role of therapeutic use of interleukin-2 in HIV infection]. 1266 84

CD8(+) T lymphocytes can inhibit human immunodeficiency virus type 1 (HIV-1) replication by secreting a soluble factor(s) known as CD8(+) T-lymphocyte antiviral factor (CAF). One site of CAF action is inhibition of HIV-1 RNA transcription, particularly at the step of long terminal repeat (LTR)-driven gene expression. The inhibitory effect of CAF on HIV-1 LTR activation is mediated through STAT1 activation. A recent study reports that alpha-defensins 1 to 3 account for CAF activity against HIV-1. Here, we address whether alpha-defensins, particularly alpha-defensin-1, contribute to CAF-mediated inhibition of HIV-1 transcription. Both recombinant alpha-defensin-1 and CAF derived from herpesvirus saimiri (HVS)-transformed CD8(+) cells inhibited HIV-1 infection and gene expression. For both factors, the inhibition of HIV-1 infection did not occur at the level of viral entry. Pretreatment of cells with alpha-defensin-1 followed by a washing out prior to infection blocked infection by HIV-1, indicating that direct inactivation of virions was not required for its inhibitory effect. In contrast to CAF, alpha-defensin-1 did not inhibit phorbol myristate acetate- or Tat-mediated HIV-1 LTR activation in a transient transfection system, nor did it activate STAT1 tyrosine phosphorylation. Furthermore, alpha-defensins 1 to 3 were below the level of detection in a panel of HVS-transformed CD8(+) cells with potent HIV-1 inhibitory activity and a neutralizing antibody against alpha-defensins 1 to 3 did not reverse the inhibitory effect of CAF on HIV-1 gene expression in infected cells and on HIV-1 LTR activation in transfected cells. Taken together, our results suggest that alpha-defensin-1 inhibits HIV-1 infection following viral entry but that alpha-defensins 1 to 3 are not responsible for the HIV-1 transcriptional inhibition by CAF.
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PMID:CAF-mediated human immunodeficiency virus (HIV) type 1 transcriptional inhibition is distinct from alpha-defensin-1 HIV inhibition. 1276 98


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