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

Human foamy virus (HFV) encodes the transcriptional transactivator bel1. The bel1 protein transactivates HFV long terminal repeat (LTR)-directed gene expression by recognizing a region in U3. It also transactivates human immunodeficiency virus type 1 (HIV-1) LTR-directed gene expression in transient transfection assays. To identify the specific region in HIV-1 LTR responsible for bel1 action, we examined the effect of bel1 on chloramphenicol acetyltransferase (CAT) gene expression in transfected cells with a series of mutant HIV-1 LTR/CAT plasmids. The region between -158 and -118 from the transcription initiation site, immediately upstream of the core enhancer element, was identified as responsible for the transactivation by bel1. In addition, bel1 transactivated a heterologous promoter when this region was positioned upstream of it in the sense and antisense orientations. Optimal transactivation of the HIV-1 LTR by bel1 did not require an intact TAR sequence, suggesting that the binding of tat to the TAR sequence is not a prerequisite for bel1 function in HIV-1 LTR-directed gene expression. In the region of the HIV-1 LTR that is necessary for the bel1-mediated transactivation, we have found a sequence which is conserved between HIV-1 and HFV. Our results suggest that the bel1 action on HIV-1 seems to be mediated by a specific DNA sequence which is shared by both the HIV-1 LTR and HFV LTR.
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PMID:Transactivation of human immunodeficiency virus type 1 long terminal repeat-directed gene expression by the human foamy virus bel1 protein requires a specific DNA sequence. 131 28

A specific RNA sequence located in the leader of all human immunodeficiency virus type 1 (HIV-1) mRNAs termed the transactivation response element, or TAR, is a primary target for induction of HIV-1 long terminal repeat activity by the HIV-1-derived trans-regulatory protein, Tat. Human neurotropic virus, JC virus (JCV), a causative agent of the degenerative demyelinating disease progressive multifocal leukoencephalopathy, contains sequences in the 5' end of the late RNA species with an extensive homology to HIV-1 TAR. In this study, we examined the possible role of the JCV-derived TAR-homologous sequence in Tat-mediated activation of the JCV late promoter (Tada et al., Proc. Natl. Acad. Sci. USA 87:3479-3483, 1990). Results from site-directed mutagenesis revealed that critical G residues required for the function of HIV-1 TAR that are conserved in the JCV TAR homolog play an important role in Tat activation of the JCV promoter. In addition, in vivo competition studies suggest that shared regulatory components mediate Tat activation of the JCV late and HIV-1 long terminal repeat promoters. Furthermore, we showed that the JCV-derived TAR sequence behaves in the same way as HIV-1 TAR in response to two distinct Tat mutants, one of which that has no ability to bind to HIV-1 TAR and another that lacks transcriptional activity on a responsive promoter. These results suggest that the TAR homolog of the JCV late promoter is responsive to HIV-1 Tat induction and thus may participate in the overall activation of the JCV late promoter mediated by this transactivation.
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PMID:Evidence that a sequence similar to TAR is important for induction of the JC virus late promoter by human immunodeficiency virus type 1 Tat. 133 25

The activity of the human immunodeficiency virus type 1 (HIV-1) transactivation protagonists tat and TAR has been analyzed from sequential primary material. The sequences were amplified from uncultured peripheral blood mononuclear cells. Despite fluctuations within the tat and TAR quasispecies there was no obvious selection for a variant encoding more powerful transactivation components either in vivo or ex vivo, indicating that this system is not exploited during disease progression. The basal levels of the natural promoters were, depending on the cell line, two- to fourfold higher than that of the reference promoter, itself derived from ex vivo adapted HIV-1 Lai.
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PMID:Absence of selection of HIV-1 variants in vivo based on transcription/transactivation during progression to AIDS. 135 Jan 26

The abnormal isoforms of the normal cellular prion protein (PrP), also termed Scrapie-associated fibril protein, are assumed to be one causative factor of spongiform encephalopathies. The mRNA of PrP contains stem-loop structures which are very similar to the human immunodeficiency virus-1 (HIV-1) cis-acting sequence TAR within the LTR; both structures contain the pentanucleotide CUGGG in the loop, and the uridine- and adenine-bulge in the stem. In this study, using purified HIV-encoded trans-activator, Tat, and HIV-1 TAR-RNA or PrP-mRNA containing the stem-loop structure, we demonstrate by use of gel-retardation and filter binding assays that Tat binds to TAR- and PrP-RNA with the dissociation constants of 2.9 or 37.0 nM, respectively, at a molar ratio of 0.7 mol of Tat to 1 mol of RNA fragment. The Tat-RNA (TAR or PrP) complexes bind to protein(s) in the nuclear matrix, isolated from human astrocytes (glial fibrillary acidic protein positive brain cells). Infection of astrocytes with HIV-1 resulted in an increased level of PrP mRNA. The data presented led us to assume that certain sequences in the PrP mRNA might be targets for proteins acting in trans.
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PMID:Accumulation of transcripts coding for prion protein in human astrocytes during infection with human immunodeficiency virus. 135 48

An adeno-associated virus vector encoding an antisense RNA was used to transduce stable intracellular resistance to human immunodeficiency virus-1 (HIV-1) in human hemopoietic and non-hemopoietic cell lines. The antisense targets are present in all HIV-1 transcripts and include the TAR sequence, which is critical for transcription and virus replication, and the polyadenylation signal. Cell lines expressing antisense RNA showed up to 95 percent inhibition of gene expression directed by the HIV-1 long terminal repeat and greater than 99 percent reduction in infectious HIV-1 production, with no detectable cellular toxicity. Because of their efficient transcription and inability to recombine with HIV-1, adeno-associated virus vectors represent a promising form of anti-retroviral gene therapy.
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PMID:Dual-target inhibition of HIV-1 in vitro by means of an adeno-associated virus antisense vector. 135 46

The human immunodeficiency virus-1 (HIV-1) protein Tat is a potent activator of virus gene expression. Tat functions through a sequence known as TAR, located immediately downstream of the transcription start site in the long terminal repeat. Several observations suggest that cellular factors cooperate with Tat in the overall transactivating process. We have isolated a human complementary DNA from the new gene MSS1, which may encode such a cellular factor, by transcomplementation of a yeast sgv1- mutant. The MSS1 protein shares 42% sequence identity with the human TBP-1 protein, which binds Tat in vitro and suppresses Tat-mediated transactivation in vivo (ref. 6). We report here that the levels of HIV activation by Tat correlate with endogenous levels of MSS1 messenger RNA. Furthermore, we provide evidence that expression of MSS1 enhances the Tat-mediated transactivation. Our results suggest that MSS1 has a key role in activation of HIV genes regulated by Tat.
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PMID:New human gene encoding a positive modulator of HIV Tat-mediated transactivation. 137 63

A general method for large scale preparation of uniformly isotopically labeled ribonucleotides and RNAs is described. Bacteria are grown on isotopic growth medium, and their nucleic acids are harvested and degraded to mononucleotides. These are enzymatically converted into ribonucleoside triphosphates, which are used in transcription reactions in vitro to prepare RNAs for NMR studies. For 15N-labeling, E.coli is grown on 15N-ammonium sulfate, whereas for 13C-labeling, Methylophilus methylotrophus is grown on 13C-methanol, which is more economical than 13C-glucose. To demonstrate the feasibility and utility of this method, uniformly 13C-labeled ribonucleotides were used to synthesize a 31 nucleotide HIV TAR RNA that was analyzed by 3D-NMR. This method should find widespread use in the structural analysis of RNA by NMR.
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PMID:Preparation of isotopically labeled ribonucleotides for multidimensional NMR spectroscopy of RNA. 138 28

Short basic peptides from the HIV Tat protein bind specifically to a bulge region in TAR RNA, with a single arginine residue providing the only sequence-specific contact. The free amino acid arginine also binds specifically to TAR. Previous circular dichroism (CD) experiments suggested that peptide binding induces a conformational change in TAR. Here we confirm this observation using single arginine-containing peptides and show that arginine or guanidine binding also induces a conformational change in TAR. A peptide containing a single arginine within a stretch of histidines (CYHHHRHHHHHA) shows pH-dependent binding and a corresponding change in TAR conformation, as detected by a decrease in the CD signal at 265 nm. Arginine and guanidine, which bind to TAR with apparent Kd's of approximately 1.5 mM, induce similar CD changes. In contrast, lysine, which does not bind specifically to TAR, has no effect. Mutants of TAR that abolish specific binding (a U-->C substitution in the three-nucleotide bulge, a deletion of the bulge, or an A-U to U-A base pair change above the bulge) show no change in the CD signal upon binding of peptides, arginine, or guanidine. The results suggest that binding of a single guanidinium group to a specific site in TAR induces a change in RNA conformation.
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PMID:Circular dichroism studies suggest that TAR RNA changes conformation upon specific binding of arginine or guanidine. 138 95

The architecture of the human immunodeficiency virus type 1 (HIV-1) genome presents an intriguing dilemma for the 3' processing of viral transcripts--to disregard a canonical 'core' poly(A) site processing signal present at the 5' end of the transcript and yet to utilize efficiently an identical signal that resides at the 3' end of the message. The choice of processing sites in HIV-1 appears to be influenced by two factors: (i) proximity to the cap site, and (ii) sequences upstream of the core poly(A) site. We now demonstrate that an in vivo-defined upstream element that resides within the U3 region, 76 nucleotides upstream of the AAUAAA hexamer, acts specifically to enhance 3' processing at the HIV-1 core poly(A) site in vitro. We furthermore show that efficient in vitro 3' processing requires the RNA stem-loop structure of TAR, which serves to juxtapose spatially the upstream element and the core poly(A) site. An analysis of the stability of 3' processing complexes formed at the HIV-1 poly(A) site in vitro suggests that the upstream element may function by increasing processing complex stability at the core poly(A) site.
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PMID:Activation of HIV-1 pre-mRNA 3' processing in vitro requires both an upstream element and TAR. 142 77

Among eukaryotic transcription trans-activators, the human immunodeficiency virus type 1 (HIV-1) Tat protein is exceptional in that its target site TAR is an RNA rather than a DNA sequence. Here, we confirm that fusion of Tat to the RNA-binding domain of the HIV-1 Rev protein permits the efficient activation of an HIV-1 long terminal repeat (LTR) promoter in which critical TAR sequences have been replaced by RNA sequences derived from the HIV-1 Rev response element (RRE). An RRE target sequence as small as 13 nucleotides is shown to form an effective in vivo target for Rev binding. More important, a fusion protein consisting of Rev attached to the VP16 transcription activation domain was also observed to efficiently activate the HIV-1 LTR from this nascent RNA target. These data demonstrate that trans-activation of transcription by acidic activation domains does not require a stable interaction with the promoter DNA and suggest that VP16, like Tat, can act on steps subsequent to the formation of the HIV-1 LTR preinitiation complex. The finding that the activation domains of VP16 and Tat are functionally interchangeable raises the possibility that these apparently disparate viral trans-activators may nevertheless act via similar mechanisms.
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PMID:The VP16 transcription activation domain is functional when targeted to a promoter-proximal RNA sequence. 142 73


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