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

Proviral integration is a required step in the retrovirus life cycle. The mechanism of integration involves specific modification of the ends of linear viral DNA and subsequent recombination with host sequences. Integration results in the limited loss of sequence information at the termini of the viral genome. The composition of the intact linear DNA termini were inferred by sequencing the 2-long terminal repeat (2-LTR) circle junction that is formed when the linear molecule undergoes intramolecular, blunt-end ligation. The junction sequence contained the nucleotides GTAC that were not present at the ends of the integrated provirus. Comparison with the sequence of the LAV-1 strain of HIV-1 demonstrated that the GT dinucleotide derived from the right-hand terminus (U5) of the linear viral DNA and the AC dinucleotide came from the left-hand terminus (U3). Therefore, the corrected size of the LAV-1 LTR is 637 bp. This conclusion was confirmed independently by assessing the structure of linear viral DNA in acutely infected T cells. A portion of the population of linear HIV-1 DNA molecules were specifically deleted at their 3' ends; the extent of this deletion was 2 bases. This result is consistent with the activity of viral integrase protein on linear viral DNA and it accounts for the structure of integrated HIV-1 proviruses.
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PMID:Two bases are deleted from the termini of HIV-1 linear DNA during integrative recombination. 223 79

To examine the restriction of HIV growth in murine cells, we infected NIH 3T3 cells with HIV pseudotyped by Moloney murine leukemia virus. The virus, which carried a dominant selectable marker under the control of the HIV LTR, gave large numbers of resistant clones, showing that murine cells are permissive for HIV uncoating, reverse transcription, nuclear transport and integration. However, we found that several murine cell lines, as well as CHO cells, could not support the function of rev, the viral regulatory gene which, in human cells, induces the cytoplasmic expression of the incompletely spliced class of HIV mRNAs that encode the viral structural proteins. Transfection of the HIV-infected murine cells with a HTLV-1 rex-expressing vector failed to rescue the rev- phenotype, indicating that the block extended to rex function. Most importantly, we could complement the rev defect by fusing the infected murine with uninfected human cells. We conclude that HIV tropism is partly a consequence of a trans-acting cellular factor critical for Rev function.
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PMID:A human cell factor is essential for HIV-1 Rev action. 224 69

Infection by human immunodeficiency virus (HIV) is followed in many cases by a clinically quiescent or latent phase that appears to continue as long as host antiviral defense is intact. This has raised the possibility that certain host susceptibility factors (i.e., environmental cofactors) might influence the progression of the disease. In this study we demonstrate that morphine can function to activate HIV/LTR-CAT fusion gene (HIV-long terminal repeat-chloramphenicol acetyltransferase) when transfected into undifferentiated human SH-SY5Y neuroblastoma cells. The stimulatory effect of morphine is amplified in SH-SY5Y cells that have been induced to differentiate first with phorbol 12-myristate 13-acetate (PMA) and is much less in cells differentiated with retinoic acid (RA). Morphine does not appreciably activate HIV/LTR-CAT expression in human MOLT-3 and other T cells. Morphine activation of HIV/LTR-CAT in the SH-SY5Y cells is not reversible by naltrexone and appears to involve a Fos/Jun signaling system. Our results suggest that narcotics such as morphine may lead to activation of latent HIV infection. This may be particularly important in tissues, such as brain, which can host latent HIV infection and which is uniquely damaged in patients with acquired immunodeficiency syndrome (AIDS) as evidenced by neuronal degeneration and dementia. We also predict that these findings may have important implications for the pathogenesis of AIDS, particularly in opiate drug abusers.
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PMID:Morphine-induced transactivation of HIV-1 LTR in human neuroblastoma cells. 225 36

The activation of nuclear factor kappa B (NF-kappa B) has been implicated in the regulation of transcription of a variety of genes and has been shown to be essential for the expression of genes controlled by the long terminal repeat of human immunodeficiency virus (HIV LTR). We show here that intracellular thiol levels play a key role in regulating this process. That is, stimulation with tumor necrosis factor alpha and/or phorbol 12-myristate 13-acetate activates NF-kappa B and markedly decreases intracellular thiols; N-acetyl-L-cysteine, an efficient thiol source, prevents this thiol decrease and blocks the activation of NF-kappa B; and the lack of activated NF-kappa B prevents the activation of the HIV LTR and the transcription of genes under its control. These findings reveal a previously unrecognized genetic regulatory mechanism in which cytokine-induced shifts in intracellular thiol levels are crucial in the control of NF-kappa B activity and thereby influence the spectrum of genes expressed by cytokine-stimulated cells.
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PMID:Intracellular thiols regulate activation of nuclear factor kappa B and transcription of human immunodeficiency virus. 226 44

We describe an unusual element that activates the synthesis of short transcripts from a wide variety of mRNA and small nuclear RNA (snRNA) promoters, including the U6 RNA polymerase III promoter. This inducer of short transcripts (IST) is located between positions -5 and +82 relative to the cap site in the HIV-1 LTR. In the presence of IST, the total transcriptional activity of the different promoters is greatly increased, but the resulting additional RNA molecules are short, ending around position +60. IST is not the RNA target (TAR) for Tat trans-activation; however, because it relies entirely on cellular factors for activity, IST may serve to provide abundant RNA targets for Tat trans-activation without a requirement for full-length viral mRNA expression.
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PMID:The HIV-1 long terminal repeat contains an unusual element that induces the synthesis of short RNAs from various mRNA and snRNA promoters. 226 26

Infection of cells by HIV can result in a period of quiescence or latency which may be obviated by treatment with inducing agents such as 5-azacytidine. Evidence from these experiments demonstrate the existence of two CpG sites in the HIV LTR which can silence transcription of both reporter genes (CAT) and infectious proviral DNA when enzymatically methylated. This transcriptional block was consistently overcome by the presence of the trans-activator tat without significant demethylation of the HIV LTR. These results suggest that DNA hypermethylation of the HIV LTR may change the binding characteristics between LTR sequences and cellular proteins, thereby suppressing HIV LTR transcription and modulating viral expression.
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PMID:Inactivation of the HIV LTR by DNA CpG methylation: evidence for a role in latency. 232 36

A possible role of DNA methylation as a factor in HIV latency was studied by methylating a HIV1-LTR-CAT plasmid in vitro and measuring its expression after transfection on Vero cells. Methylation with a eukaryotic DNA methylase resulted in a 70% inhibition of chloramphenicol acetyltransferase expression, in the absence as well as in the presence of the HIV1 trans-activator protein TAT in the cell. A similar degree of transcription inhibition was obtained by methylation of the only Hpa II site at position-143 in the HIV1-LTR with the bacterial Hpa II methylase. In contrast to the effect by eukaryotic methylation, the inhibition by Hpa II methylation could be partially reversed by cotransfection of the TAT gene. The reason may lie in an about 40% demethylation at the Hpa II site which was concomitantly observed.
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PMID:Transcription of HIV1 is inhibited by DNA methylation. 232 94

Viral infection of immunocompetent cells always leads to disordered regulation of the immune system. Thus, infection by HIV1 (human immunodeficiency virus, type 1) of mononuclear phagocytes and lymphocytes is linked to the induction of the acquired immunodeficiency syndrome (AIDS). HIV1 replication in mononuclear phagocytes appears to be dependent on both the stage of maturation and on differentiation of mononuclear phagocytes. Because of the heterogeneity of the mononuclear phagocyte system, the U937 cell line provides a convenient model for studying the regulation of HIV1 replication in mononuclear phagocytes and the involvement of these cells in the immunopathogenesis of HIV1. We have shown that endogenous interferon alpha (IFN alpha) restricted viral replication in these promonocytic cells, probably by acting on proviral transcription and by interfering with transcriptional factors involved in the transactivation of the LTR (long terminal repeat) of HIV1. Indeed, addition of a monoclonal antibody to IFN alpha U937 cells cotransfected with a LTR HIV linked to the bacterial chloramphenicol acetyl transferase (CAT) gene, together with a tat expression vector, leads to an increase in CAT activity. Conversely, the addition of IFN alpha to cells cotransfected with the same vectors is followed by a decrease in CAT activity. Finally, recent experiments indicate that chronically HIV-1-infected U937 cells are more differentiated than uninfected U937 cells, suggesting that viral gene expression is able to trigger the maturation process of the promonocytic cells towards a stage where viral transcription may escape IFN alpha. These results suggest that the first replicative cycle of HIV1 in monocytes/macrophages could be a unique target for therapeutic strategies based on the use of IFN alpha.
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PMID:Regulation of HIV1 replication in promonocytic U937 cells. 234 13

The termini of integrated retroviral DNAs are characterized by highly conserved dinucleotide sequences: 5'TG...//...CA3'. For the avian and murine C-type retroviruses, the dinucleotide sequences reside two deoxynucleotides (usually AA and TT) from the LTR ends of unintegrated viral DNA (5' AATG...//...CATT3'). The number and identity of terminal deoxynucleotides in unintegrated HIV-1 linear DNA that extend beyond the conserved dinucleotides have not been determined. However, they had been presumed to consist of a single nucleotide (5'CTG...//...CAG3') on each end, based on inspection of the nucleotide sequence between the end of the supposed primer sites for retroviral DNA synthesis and the conserved proviral termini. We have utilized the polymerase chain reaction (PCR) to amplify segments representing the joined ends of linear DNA present in covalently closed circular HIV-1 DNA molecules isolated from infected T cells. These fragments were cloned and the nucleotide sequence of the LTR-LTR circle junction of several independent clones determined. Based upon the results, we predict that, like the avian and murine viruses, HIV-1 linear DNA contains two nucleotides beyond the conserved dinucleotides: 5'ACTG...//...CAGT3'. Models for the origin of these termini and other observed junction sequences are proposed.
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PMID:Terminal nucleotides of the preintegrative linear form of HIV-1 DNA deduced from the sequence of circular DNA junctions. 238 63

Nuclear factor of activated T-cells (NFAT-1) is a transcription factor which is considered to be an important regulator in early T-cell activation. We have developed a system to monitor the transcriptional activity of NFAT-1 at the single cell level in whole animals. The system is based on the use of an oligomerized NFAT-1 binding motif that directs transcription of SV40 T-antigen in transgenic mice. This report represents the first demonstration that a multimerized short binding motif can function appropriately in transgenic mice. NFAT-1 activity had previously been thought to be confined to activated T-lymphocytes upon release of intracellular calcium. By targeting NFAT-1-dependent gene expression in transgenic mice we discovered new sites of NFAT-1 activity. Besides in T-lymphocytes NFAT-1 activity could also be induced in T-lymphocyte-depleted spleen cells and purified B-lymphocytes and requires agents that both release intracellular calcium and activate protein kinase C. A difference in the time course of appearance of NFAT-1 activity between T-lymphocytes and non-T-lymphocytes was revealed. Constitutive expression was observed in a small population of cells in the dermis and some mice have developed skin lesions. Interestingly, the tissue pattern of expression of the NFAT-1 activity resembles the expression pattern described for HIV-LTR/tat transgenic mice (Vogel, J., Hinrichs, S. H., Reynolds, R. K., Luciw, P. A., and Jay, G. (1988) Nature 335, 606-611). This similarity in expression and the fact that NFAT-1 has been shown to bind functional sequences in HIV-LTR suggest a role for NFAT-1 in dermal activation of the HIV-LTR.
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PMID:Cell type specificity and activation requirements for NFAT-1 (nuclear factor of activated T-cells) transcriptional activity determined by a new method using transgenic mice to assay transcriptional activity of an individual nuclear factor. 239 47


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