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

Elevation of the levels of circulating immune complexes frequently accompanies HIV-1 infection and is a prognostic indicator of clinical progression from asymptomatic infection to AIDS. Here we report that cross-linking of Fc gamma RI or Fc gamma RII by adherent human IgG or by specific anti-Fc gamma R mAb activates HIV-1 gene expression in the human monocytic cell line BF24 and increased HIV RNA expression in monocytes from HIV infected patients as assayed by reverse transcription-PCR. In THP-1 cells, Fc gamma R cross-linking induced NF-kappa B, which is known to bind to the regulatory region of the long terminal repeat (LTR) of HIV-1 and to activate HIV-1 transcription. Anti-TNF-alpha antibody but not anti-IL-1 beta antibody strongly inhibited both the induction of HIV-1-LTR-driven transcription and the induction of NF-kappa B by Fc gamma R cross-linking. These results indicate that Fc gamma R can mediate a TNF-alpha-dependent induction of HIV-1 gene transcription and suggest that immune complexes may contribute to the pathophysiology of HIV-1 infection by augmenting viral replication in monocytes.
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PMID:Cross-linking of Fc gamma receptors activates HIV-1 long terminal repeat-driven transcription in human monocytes. 856 12

Cationic liposomes may be valuable for the delivery of anti-sense oligonucleotides, ribozymes, and therapeutic genes into human immunodeficiency virus type 1 (HIV-1)-infected and uninfected cells. We evaluated the toxicity of three cationic liposomal preparations, Lipofectamine, Lipofectin, and 1, 2-dimyristyloxypropyl-3-dimethyl-hydroxyethyl ammonium bromide (DMRIE) reagent, to HIV-infected and uninfected cells. Monocyte/macrophages were infected with HIV-1BaL and treated with liposomes in medium containing 20% fetal bovine serum (FBS) for 4 h or 24 h at 37 degree C. Uninfected monocytic THP-1 cells and chronically infected THP-1/HIV-1IIIB cells were treated with phorbol 12-myristate 13-acetate (PMA) and exposed to liposomes in the presence of 10% FBS. Toxicity was evaluated by the Alamar Blue assay and viral p24 production. The toxic effect of cationic liposomes was very limited with uninfected cells, although concentrations of liposomes that were not toxic within a few days of treatment could cause toxicity at later times. In HIV-1BaL-infected macrophages, Lipofectamine (up to 8 microM) and Lipofectin (up to 40 microM) were not toxic after a 4-h treatment, while DMRIE reagent at 40 microM was toxic. While a 4-h treatment of THP-1/HIV-1IIIB cells with the cationic liposomes was not toxic, even up to 14 days post-treatment, all three cationic liposomes were toxic to cells at the highest concentration tested after a 24-h treatment. Similar results were obtained with the Alamar Blue assay, Trypan Blue exclusion and a method that enumerates nuclei. Infected cells with relatively high overall viability could be impaired in their ability to produce virions, indicating that virus production appears to be more sensitive to treatment with the cationic liposomes than cell viability. Our results indicate that HIV-infected cells are more susceptible than uninfected cells to killing by cationic liposomes. The molecular basis of this differential effect is unknown; it is proposed that alterations in cellular membranes during virus budding cause enhanced interactions between cationic liposomes and cellular membranes.
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PMID:Human immunodeficiency virus type-1 (HIV-1) infection increases the sensitivity of macrophages and THP-1 cells to cytotoxicity by cationic liposomes. 870 87

The long terminal repeat (LTR) of human immunodeficiency virus type 1 (HIV-1) contains sequences required for the initiation of gene transcription. Among the substances known to activate the HIV-1 LTR is hydrogen peroxide (H2O2). We report here that H2O2-induced activation of the LTR in the macrophage cell line THP-1 and the lymphocyte cell line, Jurkat, is greatly increased by vanadate. Activation of the LTR by phorbol myristate acetate, tumor necrosis factor alpha, lipopolysaccharide, or Staphylococcus epidermidis extract was not increased by vanadate, indicating some selectivity for H2O2. H2O2 and vanadate also acted synergistically to increase the production of HIV-1 virions by the latently infected macrophage cell line U-1 as determined by p24 antigen release and the detection of intact virions by electron microscopy. Effects were observed at H2O2 and vanadate concentrations down to 3 x 10(-6) M, with high concentrations leading to cell toxicity. Catalase was strongly inhibitory when added prior to the interaction of H2O2 and vanadate, but was considerably less inhibitory when the H2O2 and vanadate were allowed to preincubate prior to the catalase addition. H2O2 reacts with vanadate to form peroxides of vanadate that have potent biological effects. Our findings suggest that among these is the activation of the HIV-1 LTR.
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PMID:Activation of the HIV long terminal repeat and viral production by H2O2-vanadate. 872 29

The mechanism of inhibition of HIVBa-L replication by interleukin 10 (IL-10) in primary monocytes and macrophages at various stages of maturation was investigated using semiquantitative PCR for reverse-transcribed HIV DNA, and Northern hybridization for HIV mRNA expression in comparison with extracellular p24 antigen. Pretreatment of monocytes with IL-10 markedly inhibited expression of both unspliced and spliced HIV RNA, reaching a nadir at 7 days and recovering to normal levels by 10 days after a single application. The optimum inhibitory concentration was 25 ng/ml. Less inhibition of HIV RNA expression was observed when IL-10 was added after HIV infection of monocytes and the inhibitory effect progressively declined to negligible levels as monocytes matured into macrophages over 10 days. IL-10 also downregulated the expression of cellular genes, including the transferrin receptor, 28S rRNA, and GAPDH. The kinetics of the inhibition of cellular mRNAs correlated with the inhibition of HIV RNA and also declined as monocytes matured into macrophages. In contrast, IL-10 did not inhibit cellular mRNA expression in the macrophage cell line THP-1. Neutralizing polyclonal antibody to IL-10 reversed all its inhibitory effects. Interaction of IL-10 and TNF-alpha in combination were generally antagonistic in their effects on HIV transcription. IL-10 prevented stimulation of HIV RNA expression by TNF-alpha after preincubation with monocytes for 48 hr. IL-10 had no effect on the levels of HIV cDNA or the process of initiation and completion of reverse transcription. The inhibitory effect of IL-10 on HIV replication in maturing monocytes was probably mediated mainly by inhibition of cellular gene expression and inhibition of maturation of monocytes into macrophages and their activation, with consequent downregulation of HIV mRNA.
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PMID:Inhibition of human immunodeficiency virus replication in differentiating monocytes by interleukin 10 occurs in parallel with inhibition of cellular RNA expression. 887 Aug 45

Gene expression of human immunodeficiency virus (HIV) depends on a host cellular transcription factors including nuclear factor-kappaB (NF-kappaB). The involvement of reactive oxygen intermediates (ROI) has been implicated as intracellular messengers in the inducible activation of NF-kappaB. In this study, we compared the efficacy of two antioxidants, alpha-lipoic acid (LA) and N-acetylcysteine (NAC), which are widely recognized NF-kappaB inhibitors. Here, we demonstrate that LA has a more potent activity in inhibiting NF-KappaB-mediated gene expression in THP-1 cells that have been stably transfected with a plasmid bearing a hygromycin B resistance gene under the control of HIV-1 long terminal repeat (LTR) promoter. The spontaneous activation of NF-kappaB in this cell culture system leads to expression of the hygromycin phosphotransferase gene hence rendering the cells resistance to hygromycin B. In this study, the effect of the test compounds against transcriptional activity of HIV-1 LTR was evaluated based on the degree of cellular toxicity due to the inhibitory activity on the expression of hygromycin B resistance gene in the presence of hygromycin B. We also found that 0.2 mM LA could cause 40% reduction in the HIV-1 expression from the TNF-alpha-stimulated OM 10.1, a cell line latently infected with HIV-1. On the other hand, 10 mM NAC was required to elicit the same effect. Furthermore, the initiation of HIV-1 induction by TNF-alpha was completely abolished by 1 mM LA. These findings confirm the involvement of ROI in NF-kappaB-mediated HIV gene expression as well as the efficacy of LA as a therapeutic regimen for HIV infection and acquired immunodeficiency syndrome (AIDS). Moreover, this study validates the applicability of our present assay system which we primarily designed for the screening of candidate drugs against HIV-1 gene expression.
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PMID:Alpha-lipoic acid blocks HIV-1 LTR-dependent expression of hygromycin resistance in THP-1 stable transformants. 892 35

Mycoplasma penetrans isolated from clinical specimens of AIDS patients showed potent activity in tumor necrosis factor alpha (TNF alpha) production in THP-1, U937 and J22HL60 cell lines, and in the enhancement of HIV-1 replication in a dormantly-infected J22HL60 cell line as compared with the activities of other mycoplasmas. Both activities were found in the methanol layer but not in the chloroform layer of the membrane extracted by the Bligh-Dyer method. TNF alpha production was observed in the peritoneal macrophages from both lipopolysaccharide-responsive and -unresponsive mouse strains, and was not inhibited by polymyxin B. The induction of TNF alpha production and enhancement of HIV-1 replication were strongly inhibited by Concanavalin A-Sepharose. The inhibitory effect of Concanavalin A-Sepharose was partially prevented by sugars in the order methyl-alpha-D-mannopyranoside and methyl-alpha-D-glucopyranoside but not methyl-alpha-D-galactopyranoside. Anti-human TNF alpha antibody, however, did not reduce the activity of the methanol layer to enhance HIV-1 replication, suggesting that the methanol layer could enhance HIV-1 replication directly. These results suggest that the carbohydrate derived from M. penetrans might be responsible for the progression of HIV-1 infection.
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PMID:Induction of tumor necrosis factor alpha (TNF alpha) and enhancement of HIV-1 replication in the J22HL60 cell line by Mycoplasma penetrans. 901 88

Because candidiasis and cryptococcosis are common in human immunodeficiency virus (HIV)-infected persons, the effect of Cryptococcus neoformans and Candida albicans on HIV expression in monocytic cells was examined. Stimulation of the latently HIV-infected myelomonocytic cell line OM-10.1 with C. neoformans and C. albicans in the presence of pooled human serum caused a ratio-dependent increase in HIV production. Induction of HIV by C. neoformans was enhanced by anti-capsular antibody, while induction by both organisms was inhibited by anti-TNF-alpha antibody. In THP-1 cells transfected with HIV plasmid constructs, both organisms induced transcription from the HIV long terminal repeat that was dependent on intact NF-kappaB binding sequences. Thus, C. neoformans and C. albicans enhance HIV expression in monocytic cells through a TNF-alpha- and NF-kappaB-dependent mechanism. In HIV-infected patients, such enhancement may further impair host immunity and could accelerate the course of HIV disease.
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PMID:Induction of human immunodeficiency virus type 1 expression in monocytic cells by Cryptococcus neoformans and Candida albicans. 923 16

The HIV-1 long terminal repeat (LTR) introduced into the macrophage cell line THP-1 and the T lymphocyte cell line Jurkat in association with the luciferase reporter gene is activated by the polar, aprotic solvents dimethylsulfoxide (DMSO), dimethylacetamide (DMAC), and dimethylformamide (DMF). These solvents also greatly potentiated the activation of the LTR in THP-1 cells by phorbol myristate acetate (PMA), tumor necrosis factor alpha (TNF-alpha), H202, and a Staphylococcus epidermidis product. Lipopolysaccharide (LPS) and lipoteichoic acid (LTA) at 1 microg/ml had no effect on the LTR in THP-1 cells unless the solvents were added. The aprotic solvents also greatly potentiated the activation of the LTR in Jurkat cells by PMA, TNF-alpha, and H202, whereas LPS, LTA, or the S. epidermidis product had no effect in the presence or absence of the solvents. DMSO, DMAC, and DMF also increased the production of intact virions by latently HIV-1-infected ACH-2, J1.1, U1, and OM10.1 cells under some experimental conditions. The use of the polar aprotic solvents DMSO, DMAC, and DMF, by amplification, may allow the better detection of a weak activator of the LTR and facilitate studies of the mechanism of activation.
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PMID:Activation of the HIV type 1 long terminal repeat and viral replication by dimethylsulfoxide and related solvents. 931 Feb 89

Bicyclams are a novel class of antiviral compounds that are highly potent and selective inhibitors of the replication of HIV-1 and HIV-2. Surprisingly, however, when the prototype compound AMD3100 was tested against M-tropic virus strains such as BaL, ADA, JR-CSF, and SF-162 in human peripheral blood mononuclear cells, the compound was completely inactive. Because of the specific and potent inhibitory effect of AMD3100 on T-tropic viruses, but not M-tropic viruses, it was verified that AMD3100 interacts with the CXC-chemokine receptor CXCR4, the main coreceptor used by T-tropic viruses. AMD3100 dose dependently inhibited the binding of a specific CXCR4 monoclonal antibody to SUP-T1 cells as measured by flow cytometry. It did not inhibit the binding of the biotinylated CC-chemokine macrophage inflammatory protein (MIP) 1alpha or MIP-1beta, ligands for the chemokine receptor CCR5 (the main coreceptor for M-tropic viruses). In addition, AMD3100 completely blocked (a) the Ca2+ flux at 100 ng/ml in lymphocytic SUP-T1 and monocytic THP-1 cells, and (b) the chemotactic responses of THP-1 cells induced by stromal cell-derived factor 1alpha, the natural ligand for CXCR4. Finally, AMD3100 had no effect on the Ca2+ flux induced by the CC-chemokines MIP-1alpha, regulated on activation normal T cell expressed and secreted (RANTES; also a ligand for CCR5), or monocyte chemoattractant protein 3 (a ligand for CCR1 and CCR2b), nor was it able to induce Ca2+ fluxes by itself. The bicyclams are, to our knowledge, the first low molecular weight anti-HIV agents shown to act as potent and selective CXCR4 antagonists.
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PMID:Inhibition of T-tropic HIV strains by selective antagonization of the chemokine receptor CXCR4. 933 78

Using a chemokine receptor model based on known receptor sequences, we identified several members of the seven transmembrane domain G-protein superfamily as potential chemokine receptors. The orphan receptor ChemR1, which has recently been shown to be a receptor for the CC chemokine I-309, scored very high in our model. We have confirmed that I-309, but not a number of other chemokines, can induce a transient Ca2+ flux in cells expressing CCR8. In addition, the human erythroleukemic cell line K562 responded chemotactically in a dose-responsive manner to this chemokine. Since several chemokine receptors have been shown to be required as coreceptors for HIV-1 infection, we asked whether human immunodeficiency virus type 1 (HIV-1) could efficiently utilize CCR8. Here we show that the CCR8 receptor can serve as a coreceptor for diverse T-cell tropic, dual-tropic, and macrophage-tropic HIV-1 strains and that I-309 was a potent inhibitor of HIV-1 envelope-mediated cell-cell fusion and virus infection. Furthermore, we show by flow cytometry and immunohistochemistry that antibodies generated against the CCR8 receptor amino-terminal peptide cross-reacted with U-87 MG cells stably expressing CCR8, THP-1 cells, HL-60 cells, and human monocytes, a target cell for HIV-1 infectivity in vivo.
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PMID:The CC chemokine I-309 inhibits CCR8-dependent infection by diverse HIV-1 strains. 941 93


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