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

The pol gene of HIV-1 is expressed as a fusion protein with the upstream gag gene product after -1 ribosomal frameshifting. To get insights into the sequence requirements for the slippery heptanucleotide, generally present at the frameshift junction, and the downstream stem-loop structure, we prepared, starting from the gag-pol boundary sequence of HIV-1, serial deletion and base substitution derivatives for both of these signals, and inserted them into the amino-terminal proximal region of the luciferase gene, but downstream of the initiation codon, in out-of-frame fashion. The results of in vitro translation studies indicate that the stem-loop is not essential even if its size influences the efficiency of ribosomal frameshifting, and that the optimum repetition number of a single nucleotide within the slippery sequence exists for efficient ribosomal frameshifting.
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PMID:RNA signals for translation frameshift: influence of stem size and slippery sequence. 764 14

We have shown that (HIV-1) replication can be regulated by interaction between glucocorticoid hormones and the viral genome; treatment of acutely infected lymphoid and monocytoid cell lines with cortisol and dexamethasone increased HIV-1 production in culture. The magnitude of this response correlated with glucocorticoid receptor (GR) and GR message in responder and non-responder cell lines. Furthermore, treatment of each of two HIV-infected cell lines with glucocorticoids led to enhancement of HIV-1 gene expression. We have identified a novel intragenic glucocorticoid response element (GRE) within the genome of HIV-1 at position +5002 in the vif open reading frame, as well as a second potential GRE, previously identified by other researchers at position -257 in the HIV-1 negative regulatory element (LTR-NRE). Our data indicate that only the motif at position +5002 represents a true GRE that confers glucocorticoid inducibility to a MMTV-luciferase reporter gene construct. The GRE located at -257 lacked significant functional activity in its native configuration in that it could bind GR but did not transactivate reporter gene constructs. However, this sequence was able to impart glucocorticoid inducibility when inverted or dimerized. These results suggest that as in the case of other retroviruses, HIV-1 has evolved to interface with the GR signal transduction pathway to gain replicative advantage in target cells.
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PMID:Identification of a novel glucocorticoid response element within the genome of the human immunodeficiency virus type 1. 768 76

In contrast to the purely enhancer-dependent effect of cytokines such as TNF on the activity of the HIV regulatory region (LTR), we observed that okadaic acid (OKA) activates HIV transcription through both the enhancer, responding to the factor NF-kappa B, and the promoter domain of the LTR. The inducibility of HIV LTR-driven luciferase expression constructs in lymphoblastoid cells stimulated by OKA depended on both functional Sp1 binding elements and the ability of the TATA box to bind the protein TBP. In both transformed and normal lymphocytes, OKA stimulation induced intense phosphorylation of the constitutively expressed Sp1 protein in the nucleus, a property of OKA not shared by TNF, phorbol ester, or PHA and interleukin 2. Responsiveness of LTR constructs deleted of kappa B elements to HIV Tat expression was increased upon OKA but not TNF stimulation. Our results suggest that SP1 phosphorylation induced by OKA, a selective inhibitor of the serine-threonine phosphatase PP2A, facilitates the formation of a transcription complex involving general transcription factors, HIV Tat, and Sp1 proteins. The formation of this complex would increase, independently of an in synergy with NF-kappa B, the low basal activity of the HIV LTR observed in normal T lymphocytes.
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PMID:Induction of Sp1 phosphorylation and NF-kappa B-independent HIV promoter domain activity in T lymphocytes stimulated by okadaic acid. 774 47

We have made use of certain novel genetic elements of picornaviruses termed internal ribosomal entry sites (IRES) to construct a viral RNA with the following genetic order: PV 5' NTR-EMCV IRES-PV ORF-3' NTR (PV, poliovirus; NTR, nontranslated region; EMCV, encephalomyocarditis virus; ORF, open reading frame). Transfection of this RNA into HeLa cells yielded a poliovirus (W1-PNENPO) that contained two heterologous IRES elements (type 1 IRES of PV; type 2 IRES of EMCV) in tandem. The insertion of foreign coding sequences into the genome of W1-PNENPO between the IRES elements yielded viable polioviruses with the gene order PV 5' NTR-foreign ORF-EMCV IRES-PV ORF-3' NTR. The foreign ORFs we have employed in this study included the coding region for chloramphenicol acetyltransferase (CAT), or segments of either luciferase or the HIV-1 envelope glycoprotein gp120. W1-PV/V3-3, a dicistronic poliovirus that contained HIV-1-specific sequences that included the V3 domain of gp120, was used to infect transgenic mice (PVR+) that were engineered to express the poliovirus receptor. The genetic stability of the dicistronic viruses and the HIV-1-specific immune response in PVR+ mice after infection with these novel agents are discussed.
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PMID:Dicistronic polioviruses as expression vectors for foreign genes. 786 34

A frameshift event is necessary for expression of the products of the pol gene in a number of retroviruses, including human immunodeficiency virus type 1 (HIV-1). The basic signals necessary for frameshifting consist of a shifty sequence in which the ribosome slips and a downstream stimulatory structure which can be either a stem-loop or a pseudoknot. In HIV-1, much attention has been paid to the frameshift site itself, and only recently has the role of the downstream structure been examined. Here we used a luciferase-based experimental system to analyze in vivo the cis and trans factors potentially involved in controlling frameshifting efficiency at the gag-pol junction of HIV-1. We demonstrated that high-level frameshifting is dependent on the presence of a palindromic region located downstream of the site where the frameshift event takes place. Frameshifting efficiencies were found to be identical in mouse fibroblasts and the natural host cells of the virus, i.e., CD4+ human lymphoid cells. Furthermore, no increase in frameshifting was observed upon virus infection. Previous observations have shown that viral infection leads to specific alteration of tRNAs involved in translation of shifty sites (D. Hatfield, Y.-X. Feng, B.J. Lee, A. Rein, J.G. Levin, and S. Oroszlan, Virology 173:736-742, 1989). The results presented here strongly suggest that these modifications do not affect frameshifting efficiency.
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PMID:Translational frameshifting at the gag-pol junction of human immunodeficiency virus type 1 is not increased in infected T-lymphoid cells. 790 12

Staphylococcal strains can release a factor that strongly activates the human immunodeficiency virus type 1 (HIV-1) long terminal repeat (LTR) in THP-1 cells transfected with the HIV-1 LTR-driven luciferase reporter gene (THP-1 LTRluc). The factor is present in the overnight culture fluid and is readily released from the organisms into aqueous medium by vigorous mixing. Staphylococcal extracellular material is a complex mixture of polysaccharide and protein containing peptidoglycan and teichoic acid, released in part by cell wall turnover. The importance of the carbohydrate component is emphasized by concanavalin A (Con A) inhibition of staphylococcal product-induced LTR activation but not of activation by phorbol 12-myristate 13-acetate or tumor necrosis factor. The effect of Con A was decreased or abolished by sugars in the order methyl alpha-D-mannopyranoside > methyl alpha-D-glucopyranoside > mannose > glucose = fructose > N-acetylglucosamine. Wheat germ agglutinin was less inhibitory than Con A; in this instance N-acetylglucosamine decreased inhibition, whereas methyl alpha-D-mannopyranoside or methyl alpha-D-glucopyranoside did not. The induction of luciferase activity in THP-1 LTRluc by the staphylococcal extracellular product also was inhibited by fetal bovine and normal human serum. A comparison of 31 staphylococcal isolates (9 Staphylococcus aureus, 11 Staphylococcus epidermidis, 2 Staphylococcus haemolyticus, 4 Staphylococcus hominis, 2 Staphylococcus capitis, 2 Staphylococcus warneri, 1 Staphylococcus saprophyticus) revealed wide variation in LTR activating activity that did not correlate closely with slime production. Our findings, using induction of luciferase in THP-1 LTRluc as a model for upregulation of HIV infection, raise the possibility that staphylococci, as well as certain other microorganisms, release carbohydrate-containing exopolymers, which can activate the HIV-1 LTR, thus influencing progression of HIV infection.
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PMID:Activation of the human immunodeficiency virus long terminal repeat in THP-1 cells by a staphylococcal extracellular product. 793 1

The production and characterization of a cell line for quantitative HIV-1 Tat function and T cell activation assays is described. 1G5 is a clonal cell line derived from Jurkat T cells stably transfected with a luciferase gene driven by an HIV-1 long terminal repeat (HIV-LTR). The 1G5 clone was selected for low basal luciferase activity, susceptibility to HIV infection, and high responsiveness to Tat and T cell activation signals. A 10 to 1000-fold increase in luciferase activity after transfection or infection with tat-expressing vectors or HIV was observed. Equivalent levels of expression were detected after stimulation with T cell mitogens. The characteristics of 1G5 make it a valuable reagent for studies of HIV infection, HIV regulatory agents, and other T cell or HIV-activating factors, and for screening potential anti-HIV therapeutic agents.
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PMID:A sensitive reporter cell line for HIV-1 tat activity, HIV-1 inhibitors, and T cell activation effects. 801 90

The human immunodeficiency virus 1 (HIV-1) tat gene encodes a protein of critical importance for viral transcription. In addition, Tat has been shown capable of entering cells, stimulating cell proliferation, and altering host cell gene expression. We examined the effect of Tat on the expression of the transforming growth factor alpha (TGF-alpha) gene in MDA468 human breast carcinoma cells. We showed that these cells were capable of supporting the activation of the HIV-1 long terminal repeat by Tat. Then, in cotransfection assays, in which the TGF-alpha promoter was linked to a luciferase reporter gene and the tat gene was expressed under the control of the SV40 early promoter, we showed that tat gene expression increased TGF-alpha-luciferase reporter function but only in cells stimulated with epidermal growth factor (EGF). The effects of tat and EGF were dose dependent. To confirm these cotransfection data, Tat was expressed in Escherichia coli as a fusion protein with glutathione-S-transferase (GST) and purified on glutathione-agarose. GST-Tat was introduced into the MDA468 cells either in the presence of chloroquine or by scrape loading. The biological activity of GST-Tat was tested on cells that had been stablely transfected with the HIV-1 long terminal repeat linked to luciferase as a reporter. GST-Tat was then introduced into the cells, and the level of TGF-alpha mRNA was determined.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Human immunodeficiency virus 1 Tat stimulates transcription of the transforming growth factor alpha gene in an epidermal growth factor-dependent manner. 812 96

NF-kappa B is inducible transcription factor present in many cell types in a latent cytoplasmic form. So far, only immune cells including mature B cells, thymocytes, and adherent macrophages have been reported to contain constitutively active forms of NF-kappa B in the nucleus. A recent study showed that the human immunodeficiency virus type 1 (HIV-1) promoter is highly active in several brain regions of transgenic mice (J. R. Corboy, J. M. Buzy, M. C. Zink, and J. E. Clements, Science 258:1804-1807, 1992). Since the activity of this viral enhancer is governed mainly by two binding sites for NF-kappa B, we were prompted to investigate the state of NF-kappa B activity in neurons. Primary neuronal cultures derived from rat hippocampus and cerebral cortex showed a high constitutive expression of an HIV-1 long terminal repeat-driven luciferase reporter gene, which was primarily dependent on intact NF-kappa B binding sites and was abolished upon coexpression of the NF-kappa B-specific inhibitor I kappa B-alpha. Indirect immunofluorescence and confocal laser microscopy showed that the activity of NF-kappa B correlated with the presence of the NF-kappa B subunits p50 and RelA (p65) in nuclei of cultured neurons. NF-kappa B was also constitutively active in neurons in vivo. As investigated by electrophoretic mobility shift assays, constitutive NF-kappa B DNA-binding activity was highly enriched in fractions containing neuronal nuclei prepared from rat cerebral cortex. Nuclear NF-kappa B-specific immunostaining was also seen in cryosections from mouse cerebral cortex and hippocampus. Only a subset of neurons was stained. Activated NF-kappa B in the brain is likely to participate in normal brain function and to reflect a distinct state of neuronal activity or differentiation. Furthermore, it may explain the high level of activity of the HIV-1 enhancer in neurons, an observation potentially relevant for the etiology of the AIDS dementia complex caused by HIV infection of the central nervous system.
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PMID:Constitutive NF-kappa B activity in neurons. 819 37

The RAW264 murine macrophage cell line was used as a model to examine the role of the tat and nef gene products in the transcription regulation of the human immunodeficiency virus type 1 (HIV-1) long terminal repeat (LTR) in macrophages. Contrary to claims that the activity of the HIV-1 LTR responds poorly in rodent cells to trans activation by the viral tat gene product, cotransfection of RAW264 cells with a tat expression plasmid in transient transfection assays caused a > 20-fold increase in reporter gene expression that was inhibited by mutations in the TAR region. RAW264 cells stably transfected with the tat plasmid displayed similarly elevated HIV-1 LTR-driven reporter gene activity. By contrast to previous reports indicating a negative role for nef in HIV transcription, cotransfection of RAW264 cells with a nef expression plasmid trans activated the HIV-1 LTR driving either a chloramphenicol acetyltransferase or a luciferase reporter gene. The action of nef was specific to the LTR, as expression of nef had no effect on the activity of the simian virus 40, c-fms, urokinase plasminogen activator, or type 5 acid phosphatase promoter. trans-activating activity was also manifested by a frameshift mutant expressing only the first 35 amino acids of the protein. The effects of nef were multiplicative with those of tat gene product and occurred even in the presence of bacterial lipopolysaccharide, which itself activated LTR-directed transcription. Examination of the effects of selected mutations in the LTR revealed that neither the kappa B sites in the direct repeat enhancer nor the TAR region was required as a cis-acting element in nef action. The action of nef was not species restricted; it was able to trans activate in the human monocyte-like cell line Mono Mac 6. The presence of a nef expression cassette in a neomycin phosphotransferase gene expression plasmid greatly reduced the number of G418-resistant colonies generated in stable transfection of RAW264 cells, and many of the colonies that were formed exhibited very slow growth. The frameshift mutant was also active in reducing colony generation. Given the absence of any effect of the frameshift mutation on nef function, its actions on macrophage growth and HIV transcription are discussed in terms of the role of the N-terminal 30 amino acids and of stable secondary structures in the mRNA.
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PMID:Effects of the tat and nef gene products of human immunodeficiency virus type 1 (HIV-1) on transcription controlled by the HIV-1 long terminal repeat and on cell growth in macrophages. 823 Apr 18

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