Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0019693 (HIV)
 170,526 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Human cytomegalovirus (CMV) alters the growth and expression of human immunodeficiency virus-1 (HIV-1) in cell culture and may accelerate the course of AIDS in HIV-1 infected patients. CMV infection or the expression of the CMV immediate early genes has been shown to activate gene expression directed by the HIV-1 LTR. However, the cis-acting elements within the HIV-1 LTR that confer responsiveness to CMV have not been clearly delineated. We report on investigations in human fibroblasts designed to precisely map this signal. Our studies demonstrate that more than one nonoverlapping region of the HIV-1 promoter is capable of responding to CMV. Sequences 3' from -19(relative to the start of transcription) are dispensable for CMV responsiveness. We also show that in addition to immediate early region 2, immediate early region 1 is able to activate HIV-1 LTR-directed gene expression.
 ...
PMID:Sequence requirements for activation of the HIV-1 LTR by human cytomegalovirus. 164 74

The human spumaretrovirus (HSRV) genome contains, in addition to coding information for the structural proteins, open reading frames (ORFs) for at least three additional genes termed bel1, bel2 and bel3. We report here the localization of the transcriptional activator of HSRV to the bel1 ORF. In reporter-based transient expression assays in COS cells utilizing the bacterial CAT gene linked to HSRV LTR sequences between -710 and +309 with respect to the transcriptional initiation site, co-expression of the bel1 gene product alone caused an over 100 to 300-fold increase in the level of LTR activity. High-level trans-activation by bel1 was specific for the HSRV LTR, as relatively minor positive and negative regulatory effects were observed on HIV-1 LTR and RSV LTR expression, respectively, whereas HTLV-1 LTR activity remained unaffected. Distinct regions of the HSRV LTR were found to be involved in bel1-induced trans-activation. Specifically, deletions between -500 and -389 and between -136 and -62 in the U3 region resulted in a 4- and 30 to 35-fold decline, respectively, in the response to bel1. Limited mutagenesis of the bel1 ORF indicated that most of the bel1 coding region, except for the carboxy-terminal 27 residues, is essential for the activation function.
 ...
PMID:Distinct cis-acting regions in U3 regulate trans-activation of the human spumaretrovirus long terminal repeat by the viral bel1 gene product. 164 56

We have been studying the role of human cytomegalovirus (HCMV) as a potential cofactor in human immunodeficiency virus (HIV)-related disease. The clinical relevance of HCMV is highlighted by the fact that it is a principal viral pathogen in patients with AIDS and is known to infect the same cells as HIV. In this study, we focused on the molecular interactions between HIV and HCMV in human fibroblasts and in the human glioblastoma/astrocytoma-derived cell line U373 MG, cells which can be productively infected by both viruses. Because these cells are CD4-, we used HIV pseudotyped with a murine amphotropic retrovirus as described previously (D. H. Spector, E. Wade, D. A. Wright, V. Koval, C. Clark, D. Jaquish, and S. A. Spector, J. Virol. 64:2298-2308, 1990). Initial studies showed that when cells were preinfected with HIV (Ampho-1B) for 5 days and then superinfected with HCMV, HIV antigen production dropped significantly in the coinfected cells but continued to rise in cells infected with HIV (Ampho-1B) alone. HCMV production, however, was unaffected by the presence of HIV. Further analysis showed that HIV steady-state RNA levels and gag and env protein production were also inhibited in the presence of HCMV. The transcriptional inhibition of HIV was particularly surprising in view of the previous results of several other laboratories as well as our own that HCMV infection stimulates HIV long terminal repeat-chloramphenicol acetyltransferase (LTR-CAT) expression in transient expression assays. To investigate this further, we transfected the HIV LTR-CAT construct into either uninfected cells or cells which had been preinfected with HIV. The cells were infected with HCMV 24 h posttransfection and assayed for CAT gene expression at 48 h after HCMV infection. Although there was some stimulation of the LTR-CAT in cells that were dually infected by HIV and HCMV, it was 16-fold less than that in the cells infected only with HCMV. This suggests that in the presence of the HIV infection, the stimulation of the HIV LTR-CAT gene by HCMV is significantly reduced. Experiments with UV-irradiated HCMV and the HCMV DNA polymerase inhibitor ganciclovir showed that HCMV transcription is necessary for the reduction in HIV production to occur; however, replication of the HCMV genome or any events which take place after DNA replication are not necessary. These results, coupled with the observation that inhibition is usually first seen between 8 and 24 h after HCMV infection, suggest that an HCMV early protein is involved in repression of HIV.
 ...
PMID:Human cytomegalovirus inhibits human immunodeficiency virus replication in cells productively infected by both viruses. 165 86

In order to investigate the hypothesis that human cytomegalovirus (HCMV) influences HIV-1 infection of brain cells, we studied primary astrocytes derived from human fetal brains and a neuronal cell line (SK-N-MC). Infection of these cells with two strains of HCMV resulted in expression of immediate early, early, and late antigens and production of infectious virus. HCMV infection of primary astrocytes also led to cytopathic effects and cell death. SK-N-MC cells were infected with HIV-1 strains with or without HCMV. HIV LTR-directed CAT activities and the expression of HIV p24 antigen from the SK-N-MC culture coinfected with both HIV-1 and HCMV were higher than those from the cells infected with HIV-1 alone. The primary astrocytes were cotransfected with HIV-1 proviral DNAs and HIV LTR-CAT with or without HCMV infection. HCMV-infected astrocytes produced greater amounts of CAT activity and higher p24 than the cells transfected with HIV-1 proviral DNAs alone. When both primary astrocytes and SK-N-MC cells were transfected with (a) HIV LTR-CAT alone, (b) HIV LTR-CAT plus HCMV-IE gene, or (c) HIV LTR-CAT plus HCMV infection 2 days before the transfection, both HCMV infection and its IE gene trans-activated the HIV LTR promoter. HCMV-IE gene 2 may play a critical role in trans-activation of HIV-1 LTR.
 ...
PMID:Human cytomegalovirus infection and trans-activation of HIV-1 LTR in human brain-derived cells. 166 29

To determine whether HIV-1 tat can transactivate a heterologous promoter lacking HIV sequences other than the TAR element, TAR was placed downstream of the chicken beta-actin promoter. Tat increased expression directed by the actin-TAR promoter to a degree equal to tat induction of the HIV-1 LTR. Optimal transactivation was observed when TAR was positioned downstream of the actin promoter such that the expected cap site of transcripts from this promoter would be the same as in transcripts directed by the HIV-1 LTR. Tat was able to transactivate, though to a lesser extent, a promoter consisting solely of a TATA element fused to TAR. Thus, tat induction does not require HIV-1 LTR promoter sequences other than TAR. Tat, when fused to the DNA binding domain of BPV-1 E2, was able to transactivate a truncated SV40 promoter containing upstream E2 binding sites, indicating that tat may be capable of transactivation when directed by a DNA binding protein to an upstream site in a heterologous promoter lacking all HIV sequences. Substitution of Ala for Lys at position 41 of tat in the tat-E2 fusion, a mutation which dramatically decreases tat transactivation of the HIV-1 LTR, eliminated this transactivation.
 ...
PMID:Transactivation of heterologous promoters by HIV-1 tat. 166 14

The sequence of the LTR-LTR circle junction of human immunodeficiency virus type 1 (HIV-1) was determined. The circle junction sequences were amplified by the polymerase chain reaction and cloned into M13 sequencing vectors. The circle junction contains 4 base pairs that are not present in the integrated provirus. We show that reverse transcription in HIV-1 initiates with the addition of a dC to the tRNA primer, suggesting that the tRNA used to initiate reverse transcription ends with the consensus CCA triplet. This indicates that the source of one of the four bases in the circle junction is probably the terminal A of the tRNA primer used to initiate reverse transcription. We propose that, in HIV-1, removal of the tRNA primer by RNase H cleavage shows an unusual specificity such that cleavage occurs between the terminal rA and the adjacent rC of the tRNA primer. These data also imply that the HIV-1 integration protein removes two bases from each end of the linear viral DNA during integration as has been described for other well-studied retroviruses.
 ...
PMID:Sequence of the circle junction of human immunodeficiency virus type 1: implications for reverse transcription and integration. 169 9

HIV (human immunodeficiency virus) viraemia in serum or plasma of HIV-infected individuals was investigated by the polymerase chain reaction assay (PCR) in combination with reverse transcription to detect HIV-1 genomic RNA. Before PCR, plasma or serum was ultracentrifuged, precipitated virions were then treated with a RNase-free DNase, and a cDNA from the HIV-1 genomic RNA was synthesized. Thirty-three fresh plasma and seven sera from either HIV-1 antibody-positive individuals or patients treated with AZT were tested. Plasma from three patients were assayed 3 or 6 months apart. Twelve sera from HIV-1 antibody-negative individuals were used as negative control. PCR was performed with primers in LTR, gag and env regions: 11 of 40 samples were positive with three primer pairs, 16 with two primer pairs and 11 with only one primer pair. PCR on HIV-1 genomic cDNA was positive in 38 out of the 40 plasma or serum samples (95%), regardless of the clinical stage of the infection: HIV-1 was detected in 14 of the 15 untreated subjects and in 24 of the 25 AZT-treated patients. HIV p24 antigen was detected in the serum of 38% of subjects (15 of 40). The results suggest that this method is suitable for the detection of viral particles in plasma or serum from HIV-1-infected individuals irrespective of antiviral treatment.
 ...
PMID:The polymerase chain reaction for the detection of HIV-1 genomic RNA in plasma from infected individuals. 171 16

Analysis of molecularly cloned DNAs of SIVs isolated from Asian rhesus macaque (Macaca mulatta; SIVmac) and pig-tailed macaque (Macaca nemestrina; SIVmne) has indicated a high degree of sequence homology between these viruses. Thus SIVmac and SIVmne might have originated from the same or very closely related viruses. We have cloned and sequenced a PCR-amplified segment containing the LTR sequences of SIV originating from a stump-tailed macaque (Macaca arctoides; SIVstm). Comparative sequence analysis indicates that SIVstm belongs to the SIV/HIV-2 group; however, it is genetically distinct from the other members.
 ...
PMID:SIV of stump-tailed macaque (SIVstm) is a divergent Asian isolate. 171 4

The solution structure of the ribonuclease H domain of HIV-1 reverse transcriptase has been investigated by three-dimensional double and triple resonance heteronuclear magnetic resonance spectroscopy. The domain studied has 138 residues and comprises residues 427 to 560 of the 66 kDa reverse transcriptase with an additional four residues at the N terminus. Initial studies on the wild-type protein were hindered by severe differential line broadening, presumably due to conformational averaging. Mutation of the single tryptophan residue located in a loop at position 113 (position 535 in the reverse transcriptase sequence) to an alanine resulted in much improved spectral properties with no apparent change in structure. 1H, 15N and 13C backbone resonances were assigned sequentially using a range of three-dimensional double and triple resonance heteronuclear experiments on samples of uniformly (greater than 95%) 15N and 15N/13C-labeled protein, and the secondary structure was elucidated from a qualitative analysis of data derived from three-dimensional 15N- and 13C-edited nuclear Overhauser enhancement spectra. The secondary structure comprises three alpha-helices and five strands arranged in a mixed parallel/antiparallel beta-sheet with a +1, +1, -3x, -1x topology. The C-terminal region from residue 114 onwards appears to be conformationally disordered in solution as evidenced by an almost complete absence of sequential and medium range nuclear Overhauser effects.
 ...
PMID:Secondary structure of the ribonuclease H domain of the human immunodeficiency virus reverse transcriptase in solution using three-dimensional double and triple resonance heteronuclear magnetic resonance spectroscopy. 171 14

Tryptophan (Trp) is an indispensable amino acid required for biosynthesis of proteins, serotonin and niacin. Indoleamine 2,3-dioxygenase (IDO) is induced by infections, viruses, lipopolysaccharides, or interferons (IFNs) and this results in significant catabolism of Trp along the kynurenine (Kyn) pathway. Intracellular growth of Toxoplasma gondii and Chlamydia psittaci in human fibroblasts in vitro is inhibited by IFN-gamma and this inhibition is negated by extra Trp in the medium. Similarly, growth of a number of human cell lines in vitro is inhibited by IFN-gamma and addition of extra Trp restores growth. Thus, in some in vitro systems, antiproliferative effects of IFN-gamma are mediated by induced depletion of Trp. We find that cancer patients given Type I or Type II IFNs can induce IDO which results in decreased serum Trp levels (20-50% of pretreatment) and increased urinary metabolites of the Kyn pathway (5 to 500 fold of pretreatment). We speculate that in vivo antineoplastic effects of IFNs and clinical side effects are mediated, at least in part, by a general or localized depletion of Trp. In view of reported increases of IFNs in autoimmune diseases and our earlier findings of elevated urinary Trp metabolites in autoimmune diseases, it seems likely that systemic or local depletion of Trp occurs in autoimmune diseases and may relate to degeneration, wasting and other symptoms in such diseases. We find high levels of IDO in cells isolated from synovia of arthritic joints. IFNs are also elevated in human immunodeficiency virus (HIV) patients and increasing IFN levels are associated with a worsening prognosis. We propose that IDO is induced chronically by HIV infection, is further increased by opportunistic infections, and that this chronic loss of Trp initiates mechanisms responsible for the cachexia, dementia, diarrhea and possibly immunosuppression of AIDS patients. In these symptoms, AIDS resembles classical pellagra due to dietary deficiency of Trp and niacin. In preliminary studies, others report low levels of Trp and serotonin, and elevated levels of Kyn and quinolinic acid in AIDS patients. The implications of these data in cancer, autoimmune diseases and AIDS are discussed.
 ...
PMID:Implications of interferon-induced tryptophan catabolism in cancer, auto-immune diseases and AIDS. 172 46


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>