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

To test the hypothesis that CD8+ T cells inhibit viral replication at the level of cellular activation, an Epstein-Barr virus (EBV)-transformed cell line (FEc1) from a simian immunodeficiency virus (SIV)-seropositive sooty mangabey monkey was transfected with a human CD4 gene and shown to be replication-competent for HIV-1, HIV-2 and SIV. Utilizing a dual-chamber culture system, it was found that inhibition of viral replication can be mediated by a soluble factor. The FEc1 cell line was transiently transfected with an LTR-driven CAT reporter gene. It was found that autologous CD8+ T cells markedly inhibited CAT activity. Furthermore, co-transfection of the FEc1 cell line with an LTR-driven tat plasmid and LTR-CAT was able to quantitatively mitigate the suppressive effect. Thus, this inhibition appears to be directed at cellular mechanisms of viral transcription. Control transfections with an LTR-driven CAT plasmid with a mutation at the NFkB binding site yielded no CAT activity, suggesting that most viral replication as measured by CAT activity is dependent, to a large extent, upon cellularly derived NFkB binding proteins.
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PMID:Inhibition of cellular activation of retroviral replication by CD8+ T cells derived from non-human primates. 838 22

The consequence of phagocytosis of Mycobacterium tuberculosis by human monocytic cells on transcription and release of human immunodeficiency virus (HIV) is unknown. In order to investigate the effects of phagocytosis of M. tuberculosis on HIV transcription, human monocytic THP-1 cells were transfected with constructs of the long terminal repeat of HIV1 or 2 linked to the chloramphenicol acetyl transferase gene (HIV LTR CAT). Following phagocytosis of M. tuberculosis by THP-1 cells maintained in non-adherent conditions, there was enhanced transcription of HIV LTR CAT. This enhancement was further potentiated when such THP-1 cells adhered to tissue culture plastic. Phagocytosis of M. tuberculosis by HIV-infected THP-1 cells in non-adherent conditions had no effect on intact HIV release. However in adherent conditions, phagocytosis of M. tuberculosis reduced release of intact virus even in the face of enhanced HIV transcription. Phagocytosis of M. tuberculosis by THP-1 cells affects HIV replication at both the transcriptional level (upregulates) and the level of viral release (down-regulates) and is modified by cellular adhesion.
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PMID:Modulation of HIV transcription in and release from human monocytic cells following phagocytosis of Mycobacterium tuberculosis. 844 81

We previously demonstrated that cellular mRNAs are degraded in CD4 positive lymphocytes infected by the human immunodeficiency virus, HIV-1, but not in cells infected by the simian lentivirus, SIV. To begin to define the molecular mechanisms underlying this RNA degradation, we have established an in vitro RNA degradation assay utilizing extracts from both infected and uninfected cells. We found that in vitro transcribed, 32P-radiolabeled actin RNA was degraded in extracts prepared from CEM, CEMx174, and C8166 cells which were infected with HIV-1. Minimal actin RNA degradation was observed in extracts prepared from uninfected cells. Similarly little degradation was observed in cell-free extracts prepared from SIV-infected cells. To determine if viral RNA sequences could impart enhanced stability to cellular RNAs in our in vitro assay, we prepared radiolabeled RNAs that contained selected viral RNA determinants. One such RNA contained the HIV-1 specific TAR (transactivating region) sequence (nucleotides 1-111) appended to a reporter CAT RNA. Like the cellular actin RNA, these TARCAT RNAs were degraded in HIV-1-infected cell extracts, but not in extracts from uninfected cells or extracts prepared from SIV-infected cells. In contrast, an RNA containing only authentic HIV-1 sequences comprising TAR and gag sequences was more stable than actin RNA in HIV-1-infected extracts. These results, taken together, suggest that the in vitro assay reproduces events that occur in vivo and provide a starting point for identifying the factor responsible for cellular RNA degradation in HIV-1-infected cells.
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PMID:Development of an in vitro mRNA degradation assay utilizing extracts from HIV-1- and SIV-infected cells. 859

The objective of this study was to assess the inhibitory effect of potential negative regulatory elements on human immunodeficiency virus (HIV)-1 long terminal repeat (LTR) activity. This was carried out by pairwise comparisons of reporter gene activities of HIV-LTR-CAT constructs differing in the presence and absence of nef sequences in transient transfection assays. Parallel transfections were performed in two persistently HIV-infected cell lines and the uninfected parental cell lines. The negative regulatory element (NRE) of the LTR did not suppress HIV LTR activity in any of the cell lines examined. However, a non-LTR-derived fragment of the nef gene had a distinct suppressive effect on activity of the full-length LTR in chronically infected astrocytoma cells. A weaker negative effect of this nef partial sequence (nps) was detected in the other cell lines with constructs lacking the NRE. The nps was capable of suppressing LTR activity in trans in chronically infected astrocytoma cells in a concentration-dependent manner. These results stress a negative role of a non-LTR nef partial sequence in a cell-specific manner. In addition, our data indicate that nps functions in trans with promoters unrelated to HIV LTR such as SV40 early and CMV immediate-early promoters.
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PMID:Down-modulation of HIV-1 LTR activity by an extra-LTR nef gene fragment. 861 97

Human adenovirus E1A oncoprotein activates or represses transcription from a variety of viral and cellular promoters by several complex mechanisms. The E1A products, 289R and 243R, have differential effects on transcription directed by the human immunodeficiency virus type 1 (HIV-1) long terminal repeat (LTR). Previous reports indicate that repression of HIV-1 LTR-directed gene expression by E1A 243R is mediated through the kappa B enhancer elements located between nucleotides -105 and -82 relative to the transcription initiation start site (+1). Results from this study suggest a novel mechanism for transcriptional repression of the HIV-1 LTR by E1A 243R that is enhancer-independent and that is mediated through basal HIV-1 promoter elements. Transient expression assays, in which 5'-truncated or site-directed mutant HIV-1 LTR-CAT reporters were tested for their response to repression mediated by wild-type or mutant 243R, demonstrate that LTR sequences upstream of -31 relative to the transcription initiation start site (+1) and inclusive of the enhancer elements are dispensable for 243R-mediated repression. The ability of 243R to repress HIV-1 basal promoter activity requires both an intact N-terminus of E1A 243R and the TATA element within the HIV-1 promoter. These results support a novel mechanism for E1A 243R-induced transcriptional repression that is enhancer-independent and that targets directly the general transcription machinery.
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PMID:TATA-dependent repression of human immunodeficiency virus type-1 transcription by the adenovirus E1A 243R oncoprotein. 863 4

Signal-dependent activation of the transcription factor NF-kappaB is dominantly regulated by degradation of IkappaB-alpha protein. However, the signaling pathways that lead to the degradation are not clear. Here we report that mitogen-activated protein kinase/extracellular signal-regulated kinase kinase (MEK) kinase, an activator of stress-activated protein kinases/jun kinase-1 (SAPKs/JNK1), is involved in such signaling pathways. The transient overexpression of MEK kinase in NIH3T3 fibroblasts activates kappaB-CAT reporter expression in a synergistic manner with TNFalpha stimulation. In contrast, overexpression of kinase-negative MEK kinase suppresses TNFalpha-induced reporter expression. The overexpression of MEK kinase suppresses the inhibitory activity of co-transfected IkappaB-alpha on the kappaB-CAT or human immunodeficiency virus-long terminal repeat-luciferase reporter expression and causes the simultaneous disappearance of the overexpressed IkappaB-alpha. The disappearance of exogenous IkappaB-alpha by the overexpression of MEK kinase is prevented by calpain inhibitor-I, an inhibitor of IkappaB-alpha degradation. These results suggest that MEK kinase is a signal mediator involved in TNFalpha-induced NF-kappaB activation and that the activation of NF-kappaB by MEK kinase is regulated through the degradation of IkappaB-alpha.
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PMID:MEK kinase is involved in tumor necrosis factor alpha-induced NF-kappaB activation and degradation of IkappaB-alpha. 866 53

Tat, the human immunodeficiency virus (HIV)-encoded transcription factor, is vital for HIV replication and transcription. Any drug that inhibits Tat's activity is a valuable candidate for chemotherapeutic applications. We show here that doxorubicin (Dox), a well-known anticancer drug and its derivative, daunomycin, inhibit the ability of Tat to activate the HIV-1 LTR. We contransfected HeLa cells with pSV40TAT and a chloramphenicol acetyltransferase gene driven by an HIV LTR promoter. CAT transcription was vigorously stimulated many fold by Tat production but the effect of Tat was inhibited by Dox in a dose-dependent manner. The transcriptional activation domain of Tat, located in its 67 amino terminal residues, remains Dox sensitive. A TAR-deleted reporter gene with a Gal binding domain is transactivated by a Gal-Tat fusion protein. This transcription complex retains a high level of activity in the presence of Dox, suggesting that Dox primarily affects RNA-Tat, rather than DNA-Tat, mediated transactivation. RNA gel mobility analysis reveals that Dox does not affect the binding of Tat to TAR-RNA in vitro but does increase the binding activity of cellular nuclear proteins with TAR-RNA. Induction or activation of such TAR-binding proteins in cells that might interfere with the activity of Tat could explain the observed inhibitory effects of Dox on Tat-activated transcription. These results suggest that Dox may have chemotherapeutic effects on HIV expression mediated through TAR RNA.
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PMID:Doxorubicin inhibits Tat-dependent transactivation of HIV type 1 LTR. 874 82

We compared the efficiency of human immunodeficiency virus (HIV-1) vectors that express a marker gene (chloramphenicol acetyltransferase, CAT) using different promoter elements. In one vector, CAT was expressed under the control of an internal murine leukemia virus (MuLV) long terminal repeat (LTR). In other vectors, CAT production was regulated by the HIV-1 LTR; these vectors also contained the HIV-1 tat gene and pol sequences reported to exert cis-acting positive effects on reverse transcription or gene expression. Vectors employing the Tat-driven HIV-1 LTR exhibited up to 500-fold greater CAT expression in Jurkat lymphocytes or human peripheral blood mononuclear cells compared with vectors using the internal MuLV LTR element as a promoter. This difference was not due to improved packaging of the vector RNA into virions, but to an improved level of gene expression in the target cells. Target cell CAT expression was two- to threefold higher for the vector containing the pol sequences and was only slightly less than that seen for a trans-complemented envdeleted provirus. These results indicate that defective HIV-1 vectors with efficiencies of gene transfer and expression comparable with that of HIV-1 itself are feasible.
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PMID:Use of cis- and trans-acting viral regulatory sequences to improve expression of human immunodeficiency virus vectors in human lymphocytes. 880 25

We have previously shown that long terminal repeats (LTRs) derived from various isolates of SIVAGM share a unique functional property. In the absence of viral Tat, all SIVAGM LTRs act as much more efficient promoters than any of the other LTRs derived from representative primate immunodeficiency viruses. In the presence of Tat, however, SIVAGM LTRs are activated relatively inefficiently. To map the elements that confer these features on the SIVAGM LTR, a number of deletion mutants were constructed, and their promoter activities were determined using a bacterial CAT gene as a marker. The results obtained indicated that various elements located in the U3 region may contribute to the high basal promoter activity and that no negative elements are present in the region. The Tat-responsive sequence TAR was localized to the R region as observed for the other LTRs. A mutant carrying a single nucleotide deletion in this region completely lost responsiveness to Tat protein.
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PMID:Functional analysis of simian immunodeficiency virus SIVAGM long terminal repeat. 887 17

Infection with human immunodeficiency virus type 1 and 2 is associated with elevated concentrations of neopterin, released in large quantities by human macrophages on stimulation with interferon gamma. Evidence has suggested a potential role of neopterin derivatives in oxygen radical-mediated processes. Here we show that the redox-sensitive transcription factors AP-1 and NF-kappaB are activated by 7,8-dihydroneopterin, either directly (AP-1), or by the synergistic action with tumor necrosis factor alpha (NF-kappaB). We could further demonstrate that 7,8-dihydroneopterin enhances HIV-1 expression as shown in transient transfection assays using HIV-1 CAT promoter-reporter gene constructs. In sera of HIV+ patients 7,8-dihydroneopterin significantly correlated with neopterin and HIV-1 p24 antigen. On the basis of our data we therefore assume that 7,8-dihydroneopterin might augment progression to higher stages of HIV-associated disease.
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PMID:trans-Activation of the HIV type 1 promoter by 7,8-dihydroneopterin in vitro. 900 2


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