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

The 5'-TAR region of HIV-1 mRNA is highly conserved amongst different HIV-1 isolates. We thus investigated the potential for in vivo targeting of the TAR RNA element by a hammerhead ribozyme. The use of the CAT reporter gene linked to the HIV1-LTR, in transient assays, reveals that a hammerhead ribozyme directed towards the first GUC of HIV-1 mRNA can efficiently inhibit CAT protein expression. We show that this inhibition is sequence-specific and probably due to a cleavage activity rather than an antisense effect. We show also that a hammerhead ribozyme that is inactive in vitro is capable of inhibiting CAT protein expression in a cellular environment. These results suggest that the targeting of the HIV-1 LTR by a hammerhead ribozyme constitutes a viable approach for anti-HIV therapy.
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PMID:Ribozyme targeting of HIV-1 LTR. 809 72

Human herpesvirus 6 (HHV-6) is a lymphotropic herpesvirus, and in vitro, it can productively infect human CD4+ T cells as HIV-1. Co-infection of T cells by HIV-1 and HHV-6 can lead to both activation of the HIV-1 promoter and acceleration of the cytopathic effects. An HHV-6 (GS) cDNA clone, pCD41, encoding for a 41-kDa nuclear protein was identified and characterized previously (Chang and Balachandran, J. Virol. 65, 2884-2894 and 7085, 1991). Sequence analyses show that this protein has significant homology with the human cytomegalovirus UL44 gene coding for the ICP36 family of early-late-class phosphoprotein. Using this cDNA as the probe, a 3.8-kb EcoRI genomic fragment encoding the HHV-6(GS)P41 was cloned and designated as pGD41. When cotransfected with the HIV LTR CAT into CV-1 cells, both the pCD41 and pGD41 clones trans-activated the HIV LTR. Sequence analyses of pCD41 indicate that there are two potential open reading frames (ORFs), A and B, which are homologous to the ORFs found in the genomic clone pGD41. Deletion constructs of the pCD41 clone demonstrated that ORF-A was critical for the HIV LTR activation. Deletion analyses of the pCD41 ORF-A and the use of promoter constructs further mapped an internal functional promoter within the pCD41 sequence that can direct the synthesis of the trans-activating protein. By using HIV LTR deletion mutants, the NF-kappa B binding sites were found to be critical for response to the pCD41 trans-activation.
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PMID:trans-activation of the HIV promoter by a cDNA and its genomic clones of human herpesvirus-6. 812 64

HHV-6 infection has been associated with several malignancies including non-Hodgkin's lymphoma and Hodgkin's disease by the presence of high antibody titer and/or the presence of HHV-6 DNA. To understand their oncogenic potential, SalI restriction fragments from HHV-6 strain U1102 were transfected into NIH3T3 cells to assess transforming ability. A 3.9-kbp SalI-L DNA fragment spanning the junction of the direct repeat left (DRL) and unique long segment (UL) regions of HHV-6 induced foci of morphologically altered cells. The SalI-L transformed NIH3T3 focal lines induced tumors in nude mice within 2 weeks. The retention of HHV-6 specific DNA observed in SalI-L transformed cells and their tumor-derived lines suggest a possible maintenance function. Since both HHV-6 infection as well as transforming fragments from other DNA viruses have been shown to transactivate the human immunodeficiency virus type 1 (HIV-1) long terminal repeat (LTR), SalI-L was examined for transactivation activity. SalI-L up-regulated HIV-1 LTR CAT 10-15 fold in both monkey CV-1 and human T Jurkat cells. The further study of the SalI-L transforming fragment exhibiting transactivation of HIV-1 LTR will elucidate whether these two activities are encoded by a single gene and will aid in the understanding of the interaction between HHV-6 and HIV-1 as it relates to progression of AIDS and/or AIDS-related malignancies.
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PMID:A transforming fragment within the direct repeat region of human herpesvirus type 6 that transactivates HIV-1. 813 19

Members of the NF-kappa B/Rel family of transcription factors are involved in the transcriptional regulation of numerous polypeptides important to the immune response and cellular growth. Several genes regulated in part by NF-kappa B/Rel such as interleukin 2, IL-2 receptor alpha, and GM-CSF are trans-activated via an indirect association with the HTLV-I Tax protein in virus-infected and transformed T cells. In this study, we have investigated the interactions between Tax and NF-kappa B/Rel in an attempt to elucidate the mechanism of Tax mediated trans-activation and its role in leukemogenesis. Transfection studies were performed in Jurkat T cells using expression vectors for individual NF-kappa B subunits and the Tax protein as well as an NF-kappa B regulated reporter plasmid. NF-kappa B proteins differentially trans-activated the HIV-1 enhancer-CAT reporter; co-expression of Tax abrogated the inhibitory effect of I kappa B alpha and a trans-dominant negative mutant of p65 (p65 delta), indicating that Tax was a trans-dominant activator of NF-kappa B-regulated genes. Co-immunoprecipitation studies with extracts from transfected cells and NF-kappa B and Tax subunit specific antibodies revealed that Tax did not co-immunoprecipitate with p50/p105, c-Rel, or I kappa B; however, antibody specific to p65 was able to co-immunoprecipitate a 40kDa protein from Tax-transfected cells. Previous studies have demonstrated a physical interaction between Tax protein and p100, indicating that Tax may preferentially associate with specific NF-kappa B proteins.
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PMID:Interactions between HTLV-I Tax and NF-kappa B/Rel proteins in T cells. 815 9

Lentiviruses vary in their dependence on a functional tat gene during their viral life cycle. To begin to understand the viral and cellular parameters controlling equine infectious anemia virus (EIAV) transactivation, we investigated Tat function and Tat and LTR structural requirements necessary for successful transactivation. EIAV Tat expression was required for detection of viral antigens from a full-length provirus. The level of transactivation by EIAV Tat as measured by LTR-CAT assays correlated well with viral antigen expression. Using horse/mouse somatic cell hybrids (SCH), a single SCH line which supported EIAV transactivation was identified, indicating that the presence of specific horse chromosomes provided cellular factors required for transactivation. Transformed cell lines from several different species were also tested and found to differ in their ability to support EIAV transactivation. A canine cell line, Cf2Th, which was permissive for EIAV transactivation, and a human cell line, HeLa, which was not permissive for EIAV transactivation, were used to map regions of the LTR and Tat that were important in cell-specific transactivation. As expected, the R region of EIAV LTR was required for transactivation by EIAV Tat in all cell lines studied. Similarly, the R region of HIV LTR was necessary for transactivation by HIV Tat. However, the composition of the U3 region also influenced transactivation in a cell-specific manner. In Cf2Th cells, replacement of EIAV U3 sequences with HIV U3 sequences resulted in high basal (nontransactivated) expression, and as a result, only a twofold increase in expression was observed in the presence of EIAV Tat. Similar studies using HIV Tat demonstrated that transactivation occurred in Cf2Th cells when either EIAV or HIV U3 sequences were present in the LTR. In contrast, transactivation by either HIV or EIAV Tat in HeLa cells required the presence of HIV enhancer sequences. These findings suggested that the ability of transactivation to occur in some cell lines may involve interactions between cell-specific transcription factors and the activation domain of Tat. For transactivation in other cell lines, Tat appeared to require more ubiquitious factors that interact with both EIAV and HIV U3 sequences.
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PMID:Cellular and viral specificity of equine infectious anemia virus Tat transactivation. 817 49

Encephalopathy and neurological disorders are a major manifestation of pediatric AIDS. Although HIV-1 can replicate in cells of neuronal and glial origin, it is yet unclear whether immature neural cells, which are present during nervous system development, can support HIV-1 replication and whether neurotrophic factors can modulate HIV-1 gene expression. In this study we show that a glial cell line with a phenotype closely resembling immature glial cells is more permissive to HIV-1 infection and replication than a neuroblastic cell line. After HIV-1 infection or after transfection of these cells with the HIV-1 LTR-CAT reporter gene alone or in the presence of Tat, both HIV-1 replication and viral gene expression progressively decrease in the neuronal cell line, while they increase in the glial cell line. In both cell types viral gene expression and replication are augmented by the addition to the cells of nerve growth factor (NGF) at concentrations which induce neuronal differentiation. However, these effects are again more evident with the glial cell type, suggesting that immature glial cells may represent one of the major targets and reservoirs of HIV-1 in the developing nervous system. As NGF and Tat act synergistically in inducing HIV-1 gene expression, these data also suggest that during development the presence of high levels of neural trophic factors may activate viral replication and render the CNS more susceptible to the deleterious effects of HIV-1 infection.
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PMID:HIV-1 gene expression and replication in neuronal and glial cell lines with immature phenotype: effects of nerve growth factor. 817 51

We report a 47 year old woman that presented to the hospital with an intracranial hypertension syndrome, a right hemiparesis and a several months history of progressive malaise and behavioral disturbances. During the hospital stay, positive HIV antibodies were detected and CAT scan showed a profound left parietal rounded hypodense lesion. The patient died 21 days after admission and the postmortem pathological study showed a deep abscess in the left basal ganglia, with recognizable Toxoplasma gondii trophozoites.
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PMID:[Cerebral abscess caused by Toxoplasma gondii and AIDS. Report of a case with anatomo-pathological study]. 819 Nov 54

We have isolated two clones (XrelA.1 and XrelA.2) from Xenopus ovary representing differentially processed mRNAs homologous throughout their translated regions to the mammalian p65 subunit of NF-kappa B. The transcripts are ubiquitously present throughout development, but are most abundant in late blastulae and gastrulae. Overproduced protein shows nuclear localisation in both oocytes and early embryos. The XrelA.2 product bound to DNA as an oligomer which was not detected in the normal embryo. Two endogenous kappa B-binding complexes were present, showing no stage-specific variation, although one was relatively deficient in posterior regions of the early neurula. They were not disrupted by dimerization with over-expressed XrelA, suggesting that they were not produced by NF-kappa B/Rel/dorsal family members. The transcriptional properties of the cloned XrelA were assayed in intact embryos by co-injecting XrelA mRNA and a linear HIV LTR-driven CAT reporter gene. CAT levels were stimulated 20-30-fold by XrelA mRNA levels in the 100 pg range, and this was wholly dependent on NF-kappa B binding sites, and largely dependent on those for SP-1. These results were remarkably reproducible and show that quantitative analysis of transcription factor function is possible in intact developing Xenopus embryos A mutant lacking the transcriptional activation domain antagonised co-injected wild-type XrelA, providing a potential dominant negative p65 mutant for interfering with NF-kappa B function in analysing NF-kappa B function in normal development.
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PMID:XrelA, a Xenopus maternal and zygotic homologue of the p65 subunit of NF-kappa B. Characterisation of transcriptional properties in the developing embryo and identification of a negative interference mutant. 819 54

A cellular assay is described in which transient high-level expression of a heterologous reporter gene (chloramphenicol acetyltransferase, CAT) driven by the HIV LTR is used to determine trans-activation in a cell line constitutively expressing Tat. The use of a parallel ELISA system to determine effects on expression of CAT and of the neomycin phosphotransferase (NPT) marker gene effectively eliminated sample variability caused by cumulative processing errors or cell culture conditions. In addition the use of cationic liposome-mediated transfection minimized delay between DNA treatment that initiates trans-activation and addition of inhibitors, thereby eliminating background expression levels in treated samples. The assay has the potential to discriminate between inhibition of trans-activation and nonspecific effects such as inhibition of transfection and cytotoxicity. It has been adapted to a 96-well format suitable for high-throughput screening of natural products and synthetic chemicals.
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PMID:A quantitative assay for trans-activation by HIV-1 Tat, using liposome-mediated DNA uptake and a parallel ELISA system. 825 35

The transcriptional activity of human immunodeficiency virus type 1 (HIV-1) is affected by many cellular factors. Homologies near the HIV-1 initiator region to the DNA-binding sequences of YY1, a multifunctional transcription factor known to regulate diverse viral and cellular promoters, suggested that YY1 might regulate HIV-1. Antibody to YY1 blocked the formation of complexes by HeLa cell nuclear extract and a DNA oligonucleotide encoding the HIV-1 initiator region. HIV-1 long terminal repeat (LTR) expression, as measured the expression of a transfected LTR-CAT reporter gene, was repressed more than 12-fold by the cotransfection of a YY1 expression vector. HIV-1 production by both COS-1 and CEM cells after transfection of an infectious molecular HIV-1 clone was repressed 7- to 20-fold by cotransfection of a YY1 expression vector. HIV-1 production was also decreased threefold in a CD4-positive lymphocyte cell line chronically infected with HIV-1 (8E5) after transfection of YY1. In situ hybridization studies confirmed that YY1 reduced HIV-1 RNA expression. YY1 may play an important role in the regulation of HIV-1 LTR expression in vivo and virus production by infected cells.
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PMID:Human transcription factor YY1 represses human immunodeficiency virus type 1 transcription and virion production. 828 93


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