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

Sodium butyrate induces gene expression directed by the human immunodeficiency virus type 1 (HIV-1) long terminal repeat (LTR) in HeLa cells. Inducible regions of the HIV-1 LTR were elucidated by using 5' and 3' LTR deletion mutants and LTR site-directed mutants within the Sp1 binding sites and the trans-activation responsive (TAR) region. Two LTR regions inducible by sodium butyrate were located: one at -117 to -103 (distal site) and one at -65 to -17 (proximal site). In HeLa cells trans-fected with pZ6neo, a biologically active HIV-1 proviral clone, sodium butyrate stimulated virus production following a 3-day treatment. Inducibility of HIV-1 gene expression by sodium butyrate was unrestricted in many human cell types, including CD4+ lymphoid cells and non-CD+ brain cells and fibroblasts. Additionally, sodium butyrate transiently induced HIV-2 LTR-directed gene expression in HeLa cells. Using the HIV-1SF-2 tat gene cotransfected with pLTR-CAT site-directed TAR mutants in HeLa cells, the boundaries of tat-trans-activation were delineated more precisely. These results suggest that the induction of HIV-1 gene expression is mediated by the interaction of sodium butyrate with cellular transcription factors that bind to the HIV-LTR.
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PMID:Mutational analysis of sodium butyrate inducible elements in the human immunodeficiency virus type I long terminal repeat. 280 Mar 38

Almost all homosexual patients with acquired immunodeficiency syndrome are also actively infected with human cytomegalovirus (HCMV). We have hypothesized that an interaction between HCMV and human immunodeficiency virus (HIV), the agent that causes acquired immunodeficiency syndrome, may exist at a molecular level and contribute to the manifestations of HIV infection. In this report, we demonstrate that the immediate-early gene region of HCMV, in particular immediate-early region 2, trans-activates the expression of the bacterial gene chloramphenicol acetyltransferase that is fused to the HIV long terminal repeat and carried by plasmid pHIV-CAT. The HCMV immediate-early trans-activator increases the level of mRNA from the plasmid pHIV-CAT. The sequences of HIV that are responsive to trans-activation by the HCMV immediate-early region are distinct from HIV sequences that required for response to the HIV tat. The stimulation of HIV gene expression by HCMV gene functions could enhance the consequences of HIV infection in persons with previous or concurrent HCMV infection.
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PMID:Immediate-early gene region of human cytomegalovirus trans-activates the promoter of human immunodeficiency virus. 282 1

Human immunodeficiency virus-1 (HIV-1), which causes AIDS (acquired immune deficiency syndrome), possesses an essential gene, tat, whose product, acting through the long terminal repeat (LTR) sequences of HIV-1, activates viral genes and replication. The mechanism by which tat trans-activates HIV genes is unclear. Some studies have reported that an increase in messenger RNA accumulation directed by the HIV-1 LTR can explain the action of tat, but others suggest that this increase in mRNA levels can only partially explain trans-activation, and that translational control mechanisms may also be involved. To test those possibilities we have established an efficient adenovirus system for delivering the HIV-1 LTR attached to a reporter gene (chloramphenicol acetyltransferase; CAT) into cells and monitoring its activity. The HIV-1 LTR expressed from this adenovirus responds to trans-activation in a HeLa cell line constitutively expressing the tat protein by increasing the transcription rate of the HIV-1 LTR and the accumulation of mRNA encoding CAT. In this system the translational efficiency of this CAT mRNA in the cell is unaffected by the presence of tat.
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PMID:Transcriptional but not translational regulation of HIV-1 by the tat gene product. 283 3

Simian immunodeficiency virus from rhesus macaques (SIVmac), like human immunodeficiency virus type 1 (HIV-1), encodes a transactivator (tat) which stimulates long terminal repeat (LTR)-directed gene expression. We performed cotransfection assays of SIVmac and HIV-1 tat constructs with LTR-CAT reporter plasmids. The primary effect of transactivation for both SIVmac and HIV-1 is an increase in LTR-directed mRNA accumulation. The SIVmac tat gene product partially transactivates an HIV-1 LTR, whereas the HIV-1 tat gene product fully transactivates an SIVmac LTR. Significant transactivation is achieved by the product of coding exon 1 of the HIV-1 tat gene; however, inclusion of coding exon 2 results in a further increase in mRNA accumulation. In contrast, coding exon 2 of the SIVmac tat gene is required for significant transactivation. These results imply that the tat proteins of SIVmac and HIV-1 are functionally similar but not interchangeable. In addition, an in vitro-generated mutation in SIVmac tat disrupts splicing at the normal splice acceptor site at the beginning of coding exon 2 and activates a site approximately 15 nucleotides downstream. The product of this splice variant stimulates LTR-directed gene expression. This alternative splice acceptor site is also used by a biologically active provirus with an efficiency of approximately 5% compared with the upstream site. These data suggest that a novel tat protein is encoded during the course of viral infection.
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PMID:Functional comparison of transactivation by simian immunodeficiency virus from rhesus macaques and human immunodeficiency virus type 1. 284 68

The synthesis of a gene for the HIV TAT protein is described using a novel approach that capitalises on the ability to synthesise oligonucleotides of greater than 100 bp in length. It involves the synthesis of large oligomers covering one strand of the desired gene in its entirety and the use of small complementary bridging and adapter oligonucleotides to direct the assembly and cloning of the large oligomers. After ligation to the cloning vector the partially single stranded intermediate is transformed directly into the recipient bacterial host where the plasmid is repaired. The synthetic tat gene has been expressed in HeLa cells and is shown to trans-activate TAR+ but not TAR- HIV LTR-CAT constructs.
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PMID:Synthesis of a gene for the HIV transactivator protein TAT by a novel single stranded approach involving in vivo gap repair. 328 69

Reducing agents such as glutathione (GSH), glutathione ester (GSE), and N-acetylcysteine (NAC) have been shown to suppress the induction of HIV expression in chronically infected cells stimulated by cytokines. We present data which show the effects of the organic thiophosphate WR-151327 on the expression of latent HIV in U1 cells. The chronically infected promonocytic cell line U1 constitutively expresses low levels of HIV that can be increased by 13-phorbol 12-myristate acetate (PMA), tumor necrosis factor alpha (TNF-alpha), and granulocyte/monocyte colony-stimulating factor (GM-CSF). WR-151327 suppressed, in dose-dependent fashion, the reverse transcriptase (RT) activity induced by TNF-alpha, GM-CSF, and PMA. The maximal decrease in RT activity was 70, 80, and 50%, respectively. Pretreatment with WR-151327 also suppressed the induction of total HIV protein synthesis, as shown by Western blot analysis. In addition, WR-151327 suppressed HIV-LTR-CAT activity in transfected human rhabdomyosarcoma cells (RD). Suppression of HIV expression by WR-151327 was observed in the absence of a cytotoxic or cytostatic effect. Incubation of WR-151327 with human recombinant TNF-alpha for 6 hr at 37 degrees C did not alter the capacity of TNF-alpha to induce the expression of HIV. Our observations further support the hypothesis that reducing agents are important in the control of HIV replication and that the clinical evaluation of WR-151327 may be indicated.
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PMID:Organic thiophosphate WR-151327 suppresses expression of HIV in chronically infected cells. 752 Nov 93

Pediatric neuro-AIDS may be the first clinical manifestation of HIV infection in children born to HIV-infected mothers. As part of the neurodevelopmental examination of children, the Clinical Adaptive Test/Clinical Linguistic and Auditory Milestone Scale (CAT/CLAMS) was investigated as a tool for pediatricians to use to monitor the development of children at risk for HIV infection. The CAT/CLAMS was found to detect neurodevelopmental differences between HIV-infected and uninfected children at 12 and 18 months of age. Good correlations were found between the CAT/CLAMS and concurrently administered Bayley Scales of Infant Development. These findings suggest that the CAT/CLAMS should be considered as a part of the neurodevelopmental examination of children at risk for pediatric neuro-AIDS.
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PMID:Neurodevelopment in pediatric HIV infection. The use of CAT/CLAMS. Clinical Adaptive Test/Clinical Linguistic and Auditory Milestone Scale. 752 39

Foscarnet (phosphonoformic acid) is a pyrophosphate analog that inhibits the replication of human immunodeficiency virus type 1 (HIV-1) in vitro and in patients with AIDS. HIV-1 resistance to foscarnet has not been reported despite long-term foscarnet therapy of AIDS patients with cytomegalovirus disease. We therefore attempted to select foscarnet-resistant HIV-1 in vitro by serial endpoint passage of virus in 400 microM foscarnet. After 13 cycles of passage in MT-2 cells, virus exhibiting > or = 8.5-fold foscarnet resistance was isolated. The reverse transcriptase (RT) from resistant virions exhibited a similar level of foscarnet resistance in enzyme inhibition assays (approximately 10-fold resistance). Foscarnet-resistant virus showed increased susceptibility to 3'-azido-3'-deoxythymidine (90-fold) and to the HIV-1-specific RT inhibitors TIBO R82150 (30-fold) and nevirapine (20-fold). DNA sequence analysis of RT clones from resistant virus revealed the coexistence of two mutations in all clones: Gln-161 to Leu (CAA to CTA) and His-208 to Tyr (CAT to TAT). Sequence analysis of six clinical HIV-1 isolates showing reduced susceptibility to foscarnet revealed the Tyr-208 mutation in two, the Leu-161 mutation in one, and a Trp-88-to-Ser or -Gly mutation in four isolates. Site-specific mutagenesis and production of mutant recombinant viruses demonstrated that the Leu-161, Ser-88, and Tyr-208 mutations reduced HIV-1 susceptibility to foscarnet 10.5-, 4.3-, and 2.4-fold, respectively, in MT-2 cells. In the crystal structure of HIV-1 RT, the Gln-161 residue lies in the alpha E helix beneath the putative deoxynucleoside triphosphate (dNTP) binding site. The Gln-161-to-Leu mutation may affect the structure of the dNTP binding site and its affinity for foscarnet. The location of the Trp-88 residue in the Beta5a strand of HIV-1 RT suggest that the Ser-88 mutation affects template-primer binding, as do several mutations that affect RT susceptibility to nucleoside analogs.
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PMID:Novel mutations in reverse transcriptase of human immunodeficiency virus type 1 reduce susceptibility to foscarnet in laboratory and clinical isolates. 754 60

The regulatory Tat protein of human immunodeficiency virus type-1 (HIV-1) exerts a pleyotropic activity on the survival and proliferation of different cell types in culture. In this report, we investigated the effect of either endogenous or exogenous Tat on Bcl-2 proto-oncogene expression and cell survival in Jurkat T-cell lines and primary peripheral blood mononuclear cells. Stable and transient transfections of Jurkat cells with the cDNA of tat and a plasmid containing Bcl-2 promoter in front of CAT (Bcl-2 Pr/CAT) stimulated CAT activity and showed an increase of Bcl-2 mRNA and protein expression. This effect was specifically related to tat, because Jurkat cells transfected with the cDNA of tat in antisense orientation, tat carrying a mutation in the amino acid cys22-gly22, or the control vector alone (pRPneo-SL3) did not show any significant difference in Bcl-2 promoter activity with respect to parental Jurkat cells. We also observed a specific correlation between tat-induced Bcl-2 gene expression and inhibition of apoptosis induced by serum withdrawal. Our results suggest that the structural integrity of the activation domain of Tat was required for the promotion of the Bcl-2 promoter and Jurkat cell survival, because a single mutation in the aminoacid cys22 was sufficient to completely block the upregulation of Bcl-2 and inhibition of apoptosis. Moreover, picomolar concentrations of native or recombinant Tat were able to upregulate Bcl-2 expression both in Jurkat and primary peripheral blood mononuclear cells, suggesting that extracellular Tat, actively released by infected cells, may also play a significant role in suppressing apoptosis. An aberrant cell survival of lymphoid cells consequent to the upregulation of Bcl-2 may represent an additional pathogenetic mechanism that could help explain both the dysregulated immune response and the frequent occurrence of hyperplastic/neoplastic disorders in HIV-1-seropositive individuals.
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PMID:The human immunodeficiency virus type-1 Tat protein upregulates Bcl-2 gene expression in Jurkat T-cell lines and primary peripheral blood mononuclear cells. 757 50

The results described in this paper demonstrate that HIV-1 gp120 can upregulate gene expression directed by the HIV-1 LTR. Briefly, exposing responder CD4+CEM-T4 ID5 cells to stimulator CEMgp120/160 expressing cells (stably transfected with HIV-1 LTR-CAT and HIV-1 gp160, respectively) resulted in the increased synthesis of the CAT enzyme. Control non-transfected CEM-T4 cells did not induce the synthesis of CAT. In addition, when the responder cell line, U937-1C5 which also contains stably transfected HIV-1 LTR-CAT plasmid was exposed to irradiated CEM gp120/160 cells, there was no synthesis of the CAT enzyme. Neither recombinant gp120 nor gp160 were able to stimulate the synthesis of CAT in the responder cells. These results indicate that the mechanism by which gp120/160 expressed on transfected cells increase CAT synthesis in responder cells may be dependent on the manner which the protein is presented in association with accessory molecules. Moreover, recombinant soluble CD4 and anti-CD4 monoclonal antibodies inhibited CEM gp120/160 induced expression of HIV-1 LTR-directed expression in CEM-1D5 cells. Based on these results we hypothesize that HIV or its envelope protein, gp120, upon interaction with its receptor, the CD4 molecule on T helper cells, transduces a signal which translates into the upregulation of the gene expression directed by the HIV-1 LTR.
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PMID:HIV-1 gp120/160 expressing cells upregulate HIV-1 LTR directed gene expression in a cell line transfected with HIV-1 LTR-reporter gene constructs. 758 Aug 40


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