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Query: UMLS:C0021051 (immunodeficiency)
 71,517 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The transactivator (tat) gene of human immunodeficiency virus (HIV) plays an essential role in the replication cycle of HIV. Previous studies have evaluated the extent and mechanistic aspects of tat-mediated transactivation using lymphoid and adherent non-lymphoid cells. We have exploited the transactivation property of the tat gene to achieve high levels of hybrid HIV resulting from recombination between HIV DNAs. For this purpose, we have generated stably transformed human rhabdomyosarcoma (RD) cell lines expressing tat gene product of HIV-1. Functional analysis of the cell lines for the presence of tat protein by transfecting HIV-long terminal repeat (LTR) linked to chloramphenicol acetyl transferase (CAT) revealed low, moderate, and high tat producer cell lines. RD-tat cell lines also showed enhanced virus production upon transfection of HIV-1 proviral DNA. Further, tat producer cell lines showed a high amount of hybrid virus in comparison to the control RD cells upon transfection of truncated viral DNAs. Thus, RD-tat cell lines would be valuable target cells for generating homogeneous viruses upon transfection of viral DNA.
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PMID:Development of RD-tat cell lines: use in HIV recombination studies. 212 54

Biological interactions between human cytomegalovirus (HCMV) and the human immunodeficiency virus type 1 (HIV-1) were analysed in transfection and infection experiments, carried out in a human osteogenic sarcoma cell line (HOS) and in the same cell line chronically infected with HCMV (E155). When HOS and E155 cells were transfected with recombinant plasmids containing the HIV long terminal repeat (LTR) linked to the bacterial chloramphenicol acetyltransferase (CAT) gene, LTR-directed CAT expression was 20 times higher in E155 cells than in HOS cells. HOS cells co-infected with HCMV and HIV-1 showed enhanced production of the HIV-1 p24 antigen. In reciprocal experiments, an increase in HCMV immediate early gene expression was observed when HCMV-infected HOS cells and E155 cells were either transfected with a recombinant plasmid containing the HIV transactivator gene (pTAT), or when infected with HIV-1. DNA hybridization analysis of E155 and HCMV-infected HOS cells revealed higher levels of HCMV DNA in cells transfected with pTAT than in cells transfected with other non-specific recombinant plasmids. E155 cells transfected with pTAT also produced higher titres of infectious HCMV than control cultures of E155 cells transfected with other recombinant plasmids, including pMTAT carrying a mutant tat gene. The functional reciprocity in vitro between HCMV and HIV is discussed with respect to its possible implications for the clinical development of AIDS.
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PMID:Reciprocal enhancement of gene expression and viral replication between human cytomegalovirus and human immunodeficiency virus type 1. 215 40

Proteins encoded by a variety of DNA viruses activate gene expression from the promoter within the long terminal repeat (LTR) of the human immunodeficiency virus type 1 (HIV-1). The mechanism by which immediate-early (IE) gene products of human cytomegalovirus (CMV) activate expression from the HIV-1 LTR was examined in transient expression assays in cultures of human cells by using plasmids containing the LTR linked to the bacterial chloramphenicol acetyltransferase (CAT) gene and a plasmid expressing the CMV IE gene. Analysis of clustered site mutations within the HIV-1 LTR revealed that sequences from nucleotides -6 to +20 (relative to the start site of transcription) are critical for responsiveness to transactivation by CMV IE gene products. This region partially overlaps the trans-acting response element (+19 to +42) required for function of the HIV-1 transactivator. The CMV IE gene was shown to increase the steady-state levels of both prematurely terminated and full-length transcripts initiated within the LTR. These results support a model in which CMV IE gene products act through a specific regulatory element in the HIV-1 LTR to increase viral transcription.
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PMID:Cytomegalovirus activates transcription directed by the long terminal repeat of human immunodeficiency virus type 1. 215 54

The Epstein-Barr virus immediate-early gene product BZLF1 transactivates the human immunodeficiency virus type 1 (HIV-1) long terminal repeat (LTR). The BZLF1 gene product caused an 18-fold increase in beta-galactosidase activity from an HIV-1 LTR lacZ expression vector, whereas the HIV-1 transactivator tat caused a 44-fold increase in beta-galactosidase activity. When cells were transfected with both BZLF1 (pEBV-Z) and tat (pTAT3) expression vectors, as well as HIV-1 LTR lacZ plasmid (pLRON), a 214-fold increase in beta-galactosidase activity was observed. This result suggests a synergistic effect of BZLF1 and tat on HIV-1 LTR-directed lacZ gene expression. Analysis of quantitative BZLF1 and tat requirements for maximal HIV-1 LTR activation indicates that BZLF1 does not reduce the amount of tat required for maximal LTR activation, as would be expected if the BZLF1 synergistic effect was due to increased tat gene expression. Thus, coordinate effects of BZLF1 and tat on the HIV-1 LTR or its transcript are probably responsible for synergistic HIV-1 LTR activation.
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PMID:The Epstein-Barr virus BZLF1 gene product activates the human immunodeficiency virus type 1 5' long terminal repeat. 217 93

The human immunodeficiency virus type 1 (HIV-1) transactivator Rev is a nuclear protein that regulates expression of certain HIV-1 transcripts by binding to an RNA target element (the RRE) present in these transcripts. A short arginine-rich sequence in Rev contains the signals required to direct this protein into nuclei, where it associates preferentially with nucleoli. We created a steroid-inducible transactivator by fusing Rev with the steroid-binding domain of the glucocorticoid receptor (GR). This Rev/GR protein remains inactive in the cytoplasm when steroids are absent, but it enters the nucleus and initiates transactivation within minutes after exposure to dexamethasone. Although the GR moiety is sufficient to transport Rev/GR into nuclei, mutation of certain residues in the arginine-rich region blocks nucleolar localization and also inhibits transactivation. We find that other mutations in this region, however, can abolish the function of Rev/GR without affecting its localization; the latter phenotype may reflect a specific defect in binding of the RRE.
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PMID:Steroid-receptor fusion of the human immunodeficiency virus type 1 Rev transactivator: mapping cryptic functions of the arginine-rich motif. 221 12

Phosphate-methylated DNA hybridizes strongly and specifically to natural DNA and RNA. Hybridization to single-stranded and double-stranded DNA leads to site-selective blocking of replication and transcription. Phosphate-methylated DNA was used to interrupt the life cycle of the human immunodeficiency virus type-1 (HIV-1), the causative agent of acquired immunodeficiency syndrome (AIDS). Both antisense and sense phosphate-methylated DNA 20-nucleotide oligomers, targeted at the transactivator responsive region and the primer binding site, caused complete inhibition of viral infectivity at a low concentration. Hybridization of phosphate-methylated DNA with folded and unfolded RNA was studied by ultraviolet and proton nuclear magnetic resonance spectroscopy. The combined results of hybridization studies and biological experiments suggest that the design of effective antisense phosphate-methylated DNA should focus on hairpin loop structures in the viral RNA. For sense systems, the 5' end of the integrated viral genome is considered to be the important target site.
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PMID:Phosphate-methylated DNA aimed at HIV-1 RNA loops and integrated DNA inhibits viral infectivity. 221 5

The human immunodeficiency virus type 1 (HIV-1) envelope protein is synthesized as a gp160 precursor that is cleaved to a 120 kDa exterior glycoprotein (gp120) and a 41 kDa transmembrane glycoprotein (gp41). The HIV-1 envelope protein was stably expressed under the control of the transactivator proteins tat and rev, in wild-type and mutant Chinese hamster ovary (CHO) cells. The mutant, ldlD, is conditionally defective for the addition of galactose and N-acetylgalactosamine to oligosaccharide chains. The effects of glycosylation modification on the HIV-1 envelope's structure and function were examined. The effects of galactosylation on the structure of the envelope proteins suggest that cleavage of the gp160 precursor into gp120 and gp41 occurs intracellularly, apparently concurrent with the addition of galactose to N-linked oligosaccharides of the envelope proteins. No evidence for O-linked glycosylation of the envelope proteins in CHO cells was observed. The envelope protein in the transfected hamster cells mediated the fusion of these cells with CD4-positive lymphocytes, and this fusogenic activity was independent of the addition of either galactose or N-acetylgalactosamine to oligosaccharides in the transfected cells.
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PMID:Glycosylation and processing of the human immunodeficiency virus type 1 envelope protein. 264 53

The human immunodeficiency virus type 1 (HIV-1) preferentially infects CD4+ T lymphocytes and may exist as a latent provirus within these cells for extended periods. The transition to a productive retroviral infection results in T-cell death and clinically may lead to the acquired immune deficiency syndrome. Accelerated production of infectious HIV-1 virions appears to be closely linked to a heightened state of T-cell activation. The transactivator (Tax) protein of the type I human T-cell leukemia virus (HTLV-I) can produce such an activated T-cell phenotype and augments activity of the HIV-1 long terminal repeat. One Tax-responsive region within the HIV-1 long terminal repeat has been mapped to a locus composed of two 10-base-pair direct repeats sharing homology with the binding site for the eucaryotic transcription factor NF-kappaB (GGGACTTTCC). Tax-expressing Jurkat T cells contain one or more inducible cellular proteins that specifically associate with the HIV-1 enhancer at these binding sites. Microscale DNA affinity precipitation assays identified a Tax-inducible 86-kilodalton protein, HIVEN86A, as one of these HIV-1 enhancer-binding factors. The interaction of HIVEN86A, and presumably other cellular proteins, with the HIV-1 enhancer appears functionally important as oligonucleotides corresponding to this enhancer were sufficient to impart Tax inducibility to an unresponsive heterologous promoter. These findings suggest that the Tax-inducible cellular protein HIVEN86A plays an important role in the transcriptional activation of the HIV-1 enhancer. These specific protein-DNA interactions may also be important for the transition of HIV-1 from a latent to a productive mode of infection. Furthermore, these findings highlight an intriguing biological interplay between HTLV-1 and HIV-1 through a cellular transcriptional pathway that is normally involved in T-cell activation and growth.
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PMID:Stimulation of the human immunodeficiency virus type 1 enhancer by the human T-cell leukemia virus type I tax gene product involves the action of inducible cellular proteins. 278 7

The replication of human immunodeficiency virus type 1 (HIV-1) requires the concerted action of two virus-encoded transactivator proteins, Tat and Rev, and is in turn moderated by the viral transcriptional repressor Nef. We show here that the phenotype of a Rev- HIV-1 provirus was nonreplicating and was distinguished by accumulation of Nef protein and reduced Tat function. Provirus defective in both the rev and nef genes (Rev-Nef-) was also nonreplicating but had normal Tat function. Trans-complementation of the Rev- mutant with Rev caused a decrease of both the steady-state level and the rate of synthesis of Nef. This was accompanied by enhanced synthesis of viral structural proteins. Rev induced even greater levels of virus production from the Rev-Nef- double mutant. In contrast, exogenous Rev did not augment virus production from wild-type provirus. Virus production from Rev- and Rev-Nef- mutants induced by Rev was repressed by exogenous Nef. The repression induced by Nef could not be reversed by exogenous Rev. The ability of Rev to modulate Nef expression solely from the provirus, and thereby relieve the Nef-mediated inhibition of transcription from the viral long terminal repeat, reveals a delicate balance of the functions of these two proteins that might underlie the switch between latency and reactivation.
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PMID:Rev-induced modulation of Nef protein underlies temporal regulation of human immunodeficiency virus replication. 278 83

The recently described human immunodeficiency virus type 2 (HIV2) is significantly divergent in sequence from the more frequently isolated human immunodeficiency virus type 1 (HIV1). Both HIV1 and HIV2 encode a transactivator that is capable of strongly stimulating expression directed by the viral long terminal repeat (LTR). Here, we define the region of the HIV2 genome encoding the transactivator and show that the specificity of the transactivator differs from that of HIV1. By deletion analysis of the HIV2-LTR, we show that both HIV1 and HIV2 transactivators require sequences within 35 to 53 bp downstream of the start of transcription. However, in order to stimulate expression at full efficiency, the HIV2 transactivator further requires sequences unique to the HIV2-LTR between nucleotides +53 and +99. Hence, HIV2 poorly transactivates the LTR of HIV1, while two divergent isolates of HIV1 will efficiently transactivate the LTR of either HIV1 or HIV2. Nonetheless, in vivo competition between the transactivators of HIV1 and HIV2 suggests that they use a common mechanism.
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PMID:The specificity of the human immunodeficiency virus type 2 transactivator is different from that of human immunodeficiency virus type 1. 282 36


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