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)

Gene expression of human immunodeficiency virus (HIV) is modulated by both cellular transcription factors, which bind to cis-acting regulatory elements in the HIV-1 long terminal repeat (LTR) and the viral transactivator, tat. The enhancer element in the HIV-1 LTR which extends from -103 to -82 is critical for gene expression. This region contains two identical 10-bp direct repeats which serve as binding sites for members of the NF-kappa B family of transcription factors. However, several other cellular transcription factors, including a group of zinc finger DNA-binding proteins, also bind to NF-kappa B and related motifs. A member of this family of transcription factors, designated PRDII-BF1 or MBP-1, is a 300-kDa cellular protein which contains two widely separated zinc finger DNA binding domains. Each of these binding domains is capable of binding to NF-kappa B or related recognition motifs. Since no functional role for this protein has been demonstrated in the regulation of viral and cellular promoters, we began studies to determine whether PRDII-BF1 could modulate HIV-1 gene expression. DNase I footprinting of the HIV-1 LTR indicated that PRDII-BF1 bound to both NF-kappa B and TAR transactivation response DNA elements. Both in vitro translation and vaccinia virus expression of PRDII-BF1 cDNA resulted in the synthesis of the full-length 300-kDa PRDII-BF1 protein. Transfection experiments, using both eucaryotic expression vectors and antisense constructs, indicated that PRDII-BF1 activated HIV-1 gene expression in both the presence and absence of tat. These results are consistent with a role for PRDII-BF1 in activating HIV-1 gene expression.
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PMID:Transcription factor PRDII-BF1 activates human immunodeficiency virus type 1 gene expression. 828 30

Adeno-associated virus type 2 (AAV-2), a human parvovirus which is apathogenic in adults, inhibits replication and gene expression of human immunodeficiency virus type 1 (HIV-1) in human cells. The rep gene of AAV-2, which was shown earlier to be sufficient for this negative interference, also down-regulated the expression of heterologous sequences driven by the long terminal repeat (LTR) of HIV-1. This effect was observed in the absence of the HIV-1 transactivator Tat, i.e., at basal levels of LTR-driven transcription. In this work, we studied the involvement of functional subsequences of the HIV-1 LTR in rep-mediated inhibition in the absence of Tat. Mutated LTRs driving an indicator gene (cat) were cointroduced into human SW480 cells together with rep alone or with double-stranded DNA fragments or RNA containing sequences of the HIV-1 LTR. The results indicate that rep strongly enhances the function of negative regulatory elements of the LTR. In addition, the experiments revealed a transcribed sequence element located within the TAR-coding sequence termed AHHH (AAV-HIV homology element derived from HIV-1) which is involved in rep-mediated inhibition. The AHHH element is also involved in down-regulation of basal expression levels in the absence of rep, suggesting that AHHH also contributes to negative regulatory functions of the LTR of HIV-1. In contrast, positive regulatory elements of the HIV-1 LTR such as the NF kappa B and SP1 binding sites have no significant influence on the rep-mediated inhibition.
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PMID:Adeno-associated virus type 2 rep gene-mediated inhibition of basal gene expression of human immunodeficiency virus type 1 involves its negative regulatory functions. 828 57

The human immunodeficiency virus type 1 (HIV-1) core promoter region, extending approximately from nucleotides -40 to +80 relative to the transcription start site, contains a complex array of putative regulatory elements, including a TATA box, an initiator element, an element between the TATA box and start site, binding sites for LBP/UBP, the TAR element, and others. However, because of this elaborate architecture, the precise boundaries and functional roles for the individual regulatory elements have not been defined. To facilitate a detailed analysis of the HIV-1 core promoter, we employed in vitro transcription assays to identify the simplest control elements that activate RNA synthesis in the context of a synthetic, heterologous promoter. Because mutations at the start site previously were shown to diminish transcription, we anticipated finding an initiator as a basic regulator. However, we have demonstrated that the HIV-1 core promoter lacks an initiator that is functionally analogous to those found in the terminal transferase and adenovirus major late promoters. In its place, we identified two elements between -6 and +30, both of which appear to be necessary for significant transcriptional activation. Unlike a strong initiator, the activity of these elements was dependent on the presence of a TATA box and on their position relative to TATA. We have called the region containing these two elements the HIV-1 SSR to distinguish it from the simple transcriptional initiator elements found in other genes.
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PMID:HIV-1 core promoter lacks a simple initiator element but contains a bipartite activator at the transcription start site. 834 Apr 7

The structure of the TAR RNA element transcribed at the 5' end of the R region of the human immunodeficiency virus is compared to the structure of its duplicate sequence in the 3' R region of the viral genome. Based on the 5'-TAR secondary structure already described, we assessed by RNase T1 primer extension assay the degree of similarity between the 5'-TAR and the 3'-TAR RNA secondary structures. We also analysed the influence of modifications in the flanking sequences. We show that the secondary structures of the 5'-TAR and the 3'-TAR are very similar and are not influenced by the flanking sequences.
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PMID:Similarity of the 5' and 3'-TAR secondary structures in HIV-1. 837 97

Persistent parvovirus B19 infections in human immunodeficiency virus type 1 (HIV-1)-infected patients have been reported. The two viruses could share common target cells. The NS1 protein of B19 regulates B19 expression and we have investigated its possible effect on the long terminal repeat (LTR) of HIV-1. In transient transfection experiments, NS1 trans-activated the expression of reporter genes under the control of the HIV-1 LTR. The effect of NS1 was apparent only in the presence of the HIV-1 Tat protein, and required intact TAR and TATA box sequences.
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PMID:Trans-activation of the long terminal repeat of human immunodeficiency virus type 1 by the parvovirus B19 NS1 gene product. 837 75

Using gel shift assays, we found that the human immunodeficiency virus type 1 (HIV-1) Tat protein (Tat-1) bound both HIV-1 and HIV-2 TAR RNAs with similar high affinities. In contrast, the HIV-2 Tat protein (Tat-2) bound only TAR-2 RNA with high affinity. We conclude that the weak in vivo activity of Tat-2 on the HIV-1 long terminal repeat that has been observed previously is likely the result of low affinity for TAR-1 RNA. Additionally, TAR-2 RNA was found to contain multiple specific binding sites for Tat proteins. GAL4-Tat fusion proteins were analyzed to compare the relative transactivation activities of Tat-1 and Tat-2 in the absence of requirements for binding to TAR RNAs. The GAL4-Tat-2 protein was found to transactivate synthetic promoters containing GAL4 binding sites at levels severalfold higher than did the GAL4-Tat-1 protein.
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PMID:TAR RNA binding properties and relative transactivation activities of human immunodeficiency virus type 1 and 2 Tat proteins. 841 40

Human immunodeficiency virus (HIV-1) gene expression is activated by the viral TAT protein that interacts with an RNA sequence, TAR, located at the 5' end of all viral mRNAs. TAT functions primarily as a transcriptional activator in mammalian cells. However, in Xenopus oocytes TAT functions primarily as a translational activator. TAR is an RNA structure comprising a partially base-paired stem, a tripyrimidine bulge in the upper stem, and an unpaired six-nucleotide loop. In vitro, TAT binds directly to the bulge with no requirement for the loop. In vivo, however, mutations in the loop abolish TAT activation of transcription and translation, implying a requirement for TAR-binding cellular factors. We now provide genetic evidence for the presence of two TAR-specific cellular factors in Xenopus oocytes. These factors display independent and mutually exclusive interactions with either the loop or the bulge region of TAR. Furthermore, by using in vivo RNA competition assays we show that the cellular factors regulate the accessibility of the TAT binding site. The fact that Xenopus oocytes contain factors that specifically interact with a human viral RNA sequence might indicate that the TAT/TAR interaction is subverting a conserved pathway in the cell.
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PMID:HIV-1 TAR RNA-binding proteins control TAT activation of translation in Xenopus oocytes. 842 67

The inducer of short transcripts, or IST, is an unusual transcriptional element located downstream of the human immunodeficiency virus type 1 (HIV-1) promoter. IST activates HIV-1 transcription, but the resulting RNAs are short and end at approximately position +59. IST, therefore, appears to promote the formation of transcription complexes that are unable to elongate efficiently. This activity contrasts with that of TAR, the target for Tat trans-activation, which upon binding of the viral protein Tat promotes the formation of transcription complexes capable of efficient elongation through the entire viral genome. We have localized and characterized the IST element. Our results indicate that IST is located mainly between positions -5 and +26, although the sequences from positions +40 to +59 also contribute to IST activity. Unlike TAR, which is an RNA element, IST appears to be a DNA element. Thus, the HIV-1 R region is a complex regulatory region with RNA and DNA elements that promote the formation of transcription complexes with different elongation properties.
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PMID:Characterization of the inducer of short transcripts, a human immunodeficiency virus type 1 transcriptional element that activates the synthesis of short RNAs. 842 90

TRBP is a human cellular protein that binds the human immunodeficiency virus type 1 TAR RNA. Here, we show that the intact presence of amino acids 247 to 267 in TRBP correlates with its ability to bind RNA. This region contains a lysine- and arginine-rich motif, KKLAKRNAAAKMLLRVHTVPLDAR. A 24-amino-acid synthetic peptide (TR1) of this sequence bound TAR RNA with affinities similar to that of the entire TRBP, thus suggesting that this short motif contains a sufficient RNA-binding activity. Using RNA probe-shift analysis, we determined that TR1 does not bind all double-stranded RNAs but prefers TAR and other double-stranded RNAs with G+C-rich characteristics. Immunoprecipitation of TRBP from human immunodeficiency virus type 1-infected T lymphocytes recovered TAR RNA. This is consistent with a TRBP-TAR ribonucleoprotein during viral infection. Computer alignment revealed that TR1 is highly homologous to the RNA-binding domain of human P1/dsI protein kinase and two regions within Drosophila Staufen. We suggest that these proteins are related by virtue of sharing a common RNA-binding moiety.
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PMID:Relatedness of an RNA-binding motif in human immunodeficiency virus type 1 TAR RNA-binding protein TRBP to human P1/dsI kinase and Drosophila staufen. 845 7

Human placenta contains a high level of 2',5'-oligoadenylate (2-5A) synthetase activity of the 100-kD form of the enzyme. About 20% of the placental 2-5A synthetase activity was found to be cytosolic, whereas the remaining 80% was released by 0.5 M KCl in the presence of detergent. Most of the enzyme activity was localized in trophoblast cells, which also contain a high level of 2-5A-dependent RNase L activity. The purified trophoblast 100-kD 2-5A synthetase was shown to be activated by human immunodeficiency virus type 1 (HIV-1) 5' RNA 1-311 and 1-707, which both contain the TAR and primer binding site (PBS) structured regions. These two HIV-1 RNAs activated human trophoblast 2-5A synthetase at the same level as poly(I).poly (C), a standard highly efficient activator of the enzyme, and at the same optimal concentration. On the contrary, HIV-1 RNA 311-618, a poorly structured region missing TAR and PBS, was shown to be a poor activator of the enzyme. The specific cellular location of the 2-5A synthetase and its efficient activation by HIV 5' RNA favors the idea that the trophoblast 2-5A system negatively controls HIV replication in trophoblasts.
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PMID:High levels of 2',5'-oligoadenylate synthetase and 2',5'-oligoadenylate-dependent endonuclease in human trophoblast. 845 85


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