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Query: UMLS:C0019693 (HIV)
 170,526 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In order to investigate the hypothesis that human cytomegalovirus (HCMV) influences HIV-1 infection of brain cells, we studied primary astrocytes derived from human fetal brains and a neuronal cell line (SK-N-MC). Infection of these cells with two strains of HCMV resulted in expression of immediate early, early, and late antigens and production of infectious virus. HCMV infection of primary astrocytes also led to cytopathic effects and cell death. SK-N-MC cells were infected with HIV-1 strains with or without HCMV. HIV LTR-directed CAT activities and the expression of HIV p24 antigen from the SK-N-MC culture coinfected with both HIV-1 and HCMV were higher than those from the cells infected with HIV-1 alone. The primary astrocytes were cotransfected with HIV-1 proviral DNAs and HIV LTR-CAT with or without HCMV infection. HCMV-infected astrocytes produced greater amounts of CAT activity and higher p24 than the cells transfected with HIV-1 proviral DNAs alone. When both primary astrocytes and SK-N-MC cells were transfected with (a) HIV LTR-CAT alone, (b) HIV LTR-CAT plus HCMV-IE gene, or (c) HIV LTR-CAT plus HCMV infection 2 days before the transfection, both HCMV infection and its IE gene trans-activated the HIV LTR promoter. HCMV-IE gene 2 may play a critical role in trans-activation of HIV-1 LTR.
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PMID:Human cytomegalovirus infection and trans-activation of HIV-1 LTR in human brain-derived cells. 166 29

The CD2 T lymphocyte glycoprotein surface molecule mediates both cell to cell adhesion and T cell activation, two processes that are involved in the spread of HIV infection. Treatment of chronically HIV-infected PBMC with anti-CD2 mAb has been shown to induce the expression of infectious virus from these cultures. In this study we investigated the mechanisms whereby anti-CD2 antibodies stimulate viral production. We demonstrate that treatment of transiently transfected T lymphocytes with anti-CD2 antibodies results in activation of the HIV long terminal repeat. Furthermore, CAT assays using mutated HIV long terminal repeat-CAT constructs and gel shift assays demonstrate that this activation is dependent on the NF-kappa B enhancer. These studies suggest that interaction of CD2 with its natural ligand, LFA-3, may play a role in regulation of HIV expression.
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PMID:Anti-CD2 receptor antibodies activate the HIV long terminal repeat in T lymphocytes. 168 Sep 14

The herpes simplex virus type 1 (HSV-1)-mediated transactivation of human immunodeficiency virus type 1 (HIV-1) provirus was studied in cell lines containing either integrated tat-defective HIV-1 provirus (HNHIVdt4 cells) or the tat-defective HIV-1 provirus, and a plasmid in which the expression of human alpha 2 interferon (HuIFN-alpha 2) was under the control of the HIV-1 long terminal repeat (LTR) (HNHIV alpha 1 cells). In both cell lines, transcription of the HIV-1 provirus was below the limits of detection, but it could be induced effectively by transfection with a HIV-1 tat-expression plasmid. In HNHIV alpha 1 cells, HuIFN-alpha 2 was induced concomitantly with HIV-1 provirus, although these cells synthesized only low levels of IFN constitutively. In contrast, infections with HSV-1 activated transcription of HIV-1 provirus only in HNHIVdt4 cells but not in HNHIV alpha 1 cells. Similarly in a transient expression assay, HSV-1 up-regulated expression of a HIV LTR-CAT (chloramphenicol acetyltransferase gene) plasmid in HNHIVdt4 but not in HNHIV alpha 1 cells. No major differences could be detected in the expression of HSV-1 immediate-early (IE) genes IE175 and IE110 (which are essential for the activation of HIV-1 LTR) in HNHIVdt4 and HNHIV alpha 1 cells to account for the inability of HSV-1 to induce HIV-1 in HNHIV alpha 1 cells. However, major differences were observed in the binding pattern of NF-kappa B-specific nuclear proteins to the enhancer region of the HIV-1 LTR: whereas binding of the 45-kDa NF-kappa B-specific nuclear protein was detected in nuclear extracts from HNHIVdt4 cells, no protein binding was seen in extracts from HNHIV alpha 1 cells. These results suggest an alternate mechanism by which IFN may alter the expression of cellular and viral genes.
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PMID:Inhibition by interferon of herpes simplex virus type 1-activated transcription of tat-defective provirus. 171 35

The adeno-associated virus (AAV) rep gene encodes four proteins (Rep78, Rep68, Rep52, and Rep40) required for AAV DNA replication and AAV gene regulation. In addition, the Rep proteins may have pleiotropic regulatory effects in heterologous systems, and in particular Rep78 may mediate a negative regulatory effect. We analyzed the effects of the AAV rep gene on human immunodeficiency virus type 1 (HIV-1) gene expression. The rep gene proteins of AAV type 2 (AAV2) inhibited the trans-activating ability of HIV-1. Constructs containing the AAV2 rep gene (pHIVrep) or a CAT gene (pBennCAT) expressed from the 5' HIV-1 long terminal repeat were inducible for Rep78 and Rep68 or CAT expression, respectively, when cotransfected with a plasmid containing the HIV-1 tat gene (pARtat). When equivalent amounts of pHIVrep and pBennCAT were cotransfected with increasing amounts of pARtat, expression of CAT activity was decreased. The pHIVrep construct was more inhibitory than plasmids expressing rep from the wild-type AAV2 p5 transcription promoter. rep expression from pHIVrep almost completely inhibited the replication of an HIV-1 proviral clone as measured by reverse transcriptase activity and p24 protein levels. Inhibition of HIV-1 production by Rep protein was also seen at the transcriptional level in that all HIV-1 transcripts were decreased when pHIVrep was present. The inhibitory effects of pHIVrep appear to be mediated primarily by Rep78 and perhaps Rep68. These results suggest that a trans-acting protein from a heterologous virus might be used to inhibit HIV-1 growth.
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PMID:Adeno-associated virus Rep protein inhibits human immunodeficiency virus type 1 production in human cells. 184 99

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

Three molecular clones of HIV-1, derived from a single isolate (AL1), exhibited distinct replicative and cytopathic properties during propagation in a human T cell line. The phenotypic differences observed were attributable, in large part, to changes affecting the viral LTR. Nucleotide sequence and PCR analyses demonstrated the presence of novel duplications or deletions involving the NF-kappa B motif. These changes in the enhancer element were identified in the original AL1 virus stock. Subcloning of the variant NF-kappa B segments into LTR-driven CAT expression vectors confirmed a correlation between promoter activity and replicative/cytopathic capacity.
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PMID:A novel HIV-1 isolate containing alterations affecting the NF-kappa B element. 199 72

The evidence presented here indicates that the domain containing the COOH-terminal part of the Saccharomyces cerevisiae SCD25 gene product (C-domain), which is homologous to the COOH-terminal part of CDC25 protein, can elicit activation of mammalian ras proteins in CHO cells. Transfection of expression vectors carrying the C-domain of SCD25, but not of CDC25, promotes the GTP-bound form of ras proteins as determined by analysis of the guanine nucleotides bound to ras proteins immunoprecipitated by Y13-259 mAb, and enhances transcription of a HIV-LTR-CAT construct. This is the first demonstration of the activation of ras proteins by transfection of a single heterologous gene.
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PMID:The COOH-domain of the product of the Saccharomyces cerevisiae SCD25 gene elicits activation of p21-ras proteins in mammalian cells. 200 Feb 28

The finding of dual HTLV-I and HIV-1 infection in populations at risk for AIDS raises the possibility that interaction between the two viruses might have clinical significance. It was shown that HTLV-I enhances HIV-1 expression, but whether HIV-1 activates HTLV-I remains to be demonstrated. To study HTLV-I behaviour following HIV-1 infection, we superinfected cells from two HTLV-I transformed cell lines with HIV-1 (strain IIIB). Viral RNA analysis indicated that HTLV-I expression in the doubly infected cells was moderately enhanced. Moreover, CAT assays in HTLV-I transformed cells transiently transfected with HTLV-I LTR-CAT disclosed higher activity in the HIV-1 superinfected cultures. This enhancement was observed only after infection with active HIV-1 virus, but not following exposure to inactivated viral particles or transfection with HIV-1 tat gene.
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PMID:Reciprocal activation of human T-lymphotropic viruses in HTLV-I-transformed cells superinfected with HIV-1. 200 72

Human immunodeficiency virus type 1 (HIV-1) NEF protein has been demonstrated to be a negative regulator of HIV-1 replication and HIV-1 LTR transcription under transient expression conditions. The difficulty of several laboratories to reproduce these findings led us to reexamine the role of NEF in HIV-1 provirus expression and HIV-1 LTR transcription. Basal transcription from the HIV-1 LTR in the presence of a NEF expression vector was compared to that in the presence of a mutated NEF vector. NEF expression led to a greater than 10-fold repression of LTR transcription under these conditions. HeLa and Jurkat cell lines carrying the nef gene linked to the CMV promoter or the HIV-1 LTR were isolated by coselection for neomycin resistance. Single cell isolates were further selected for the expression of nef transcripts. With the exception of the anti-sense nef cell lines, all the nef cell lines expressed the 27-kDa NEF protein, detectable by immunoprecipitation. NEF+ HeLa cell lines were at least 5-fold less efficient than NEF- HeLa cell lines in transient proviral expression. Provirus expression was also repressed in the NEF+ Jurkat cell lines. TAT-activated LTR transcription from an HIV-1 LTR-linked CAT expression vector was repressed 10-fold in the NEF+ HeLa and NEF+ Jurkat cell lines. When infected with HIV-1, NEF expressing T lymphoid cell lines showed moderate delays in onset and peak of reverse transcriptase production. However, none of these cell lines completely arrested virus replication. Our data confirm a negative regulatory effect of NEF on both virus production and LTR driven CAT expression in the cell lines tested. It is possible that cell specific factors may influence NEF activity.
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PMID:Human immunodeficiency virus type 1 (HIV-1) provirus expression and LTR transcription are repressed in NEF-expressing cell lines. 202 88

Transcriptional activation of gene expression directed by the long terminal repeat (LTR) of the human immunodeficiency virus type 1 (HIV-1) requires both the Tat activation response element (TAR) and the Tat protein. Mutants lacking a functional tat gene are not able to replicate. An approach we have used to suppress HIV-1 gene expression is based on the controlled overexpression of multimerized TAR sequences, which results in the sequestration of one or more components of the Tat response. Since Tat has no known cellular analog, a modified HIV-1 LTR, which is highly induced by the presence of Tat, was used to promote the expression of the multimerized TAR (poly-TAR) specifically in the presence of Tat. Cotransfection of an HIV-1 LTR-controlled poly-TAR plasmid with LTR-Tat and LTR-CAT plasmids inhibited the level of the reporter gene activity (CAT) as much as 97%. The downregulation of HIV-1 gene expression observed was dependent on the quantity of transfected poly-TAR as well as the number of tandem TAR repeats expressed per unit transcript. Similar constructs lacking either LTR upstream sequences or the TAR sequence had no significant effect, suggesting that the competitive effect was mediated at the RNA level and that it was the nascent RNA, rather than DNA, that was recognized by the Tat protein. Tat-regulated production of the poly-TAR transcript provides a means for dissecting the mechanism of Tat-mediated trans-activation of the HIV-1 LTR. The ability to regulate a viral inhibitory gene so that it is expressed only when needed should prove useful in devising an antiviral strategy through gene therapy.
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PMID:Tat-regulated production of multimerized TAR RNA inhibits HIV-1 gene expression. 203 68


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