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

The monocytic leukemic cell line U937 can be infected with human immunodeficiency virus type 1 (HIV-1) to become permanently infected virus producers. Uninfected U937 cells express T4 (CD4) antigen and form syncytia when mixed with HIV-1 producing cells. Anti-T4 monoclonal antibodies block syncytium formation indicating that the HIV-1 receptors on U937 cells include T4 antigen. The promyelocytic leukemic cell line HL60, while expressing only low amounts of surface T4 and not forming syncytia on exposure to HIV-1, can be infected by HIV-1 at lower efficiency than U937 and T-cell lines. 12-O-Tetradecanoylphorbol-13-acetate (TPA) treatment induces the differentiation of U937 cells into macrophages. HIV-infected U937 cells retain the ability to differentiate, though less efficiently, as shown by the appearance of monocyte/macrophage surface markers. T4 antigen on both U937 and T-cell lines is down regulated by TPA treatment. Functional receptors for HIV-1, assayed by syncytium induction and pseudotype plating, are lost concomitantly with T4 antigen following TPA treatment of U937 cells and T cells.
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PMID:Human immunodeficiency virus infection of monocytic and T-lymphocytic cells: receptor modulation and differentiation induced by phorbol ester. 310 14

The AIDS Surveillance System in Japan was set up in 1984 and by 1987, 29 AIDS patients had been reported. 10 were homosexuals, 16 were hemophiliacs and 3 were heterosexuals. 9 out of 16 hemophiliacs with AIDS had A-type hemophilia. 2 females were also reported as victims of AIDS. 19 patients have died 5 male homosexuals (4.4%) out of 113 (93 Japanese and 20 Foreigners) individuals were anti-HIV-positive. In 1984 sera from 65 hemophiliacs, 85 hemodialysis patients and 304 healthy volunteer blood donors were examined and 10 (15.4%) of the hemophiliacs proved to be anti-HIV positive. On the other hand, in Tokyo and Nagasaki 50-60% were positive, but in Tottori and Osaka only 25-28% were positive. The enzyme-linked immunosorbent assay (ELISA) test is widely used to detect antibodies, however, the test often gives false-positive reactions, and the blood must be reexamined by means of the Western-blot test or IF method. Therefore, a simple particle agglutination (FA) assay was developed by the authors using gelatin beads as the artificial antigen carrier. This assay is extremely sensitive as compared to IF and ELISA. Among HTLV-1/ATLV-carrying T-cell lines, all except one (TCL-As) were susceptible to HIV infection and showed cytopathic effect (CPE). HIV has quite a broad host range in vivo and in vitro. HIV was detected in brain macrophages from AIDS patients with encephalopathy. HIV may also infect nerve cells or glial cells. The MT-4 cell line was found to be most prone to HIV infection. In order to evaluate the virus-induced CPE of infected MT-4 cells, the H-thymidine incorporation method (cell proliferation assay) was developed that involved that involves measuring the survival of the cells. Inhibition of DNA synthesis in infected MT-4 cells was detected by this assay when the CPE was observed microscopically. This assay system is also useful for measuring the amount of infectious virus. Many chemicophysical agents such as suramin, antimoniotungstate (HFA-23), phosophonoformic acid, ribavirin, 3-azido-3-deoxythymidine (AZT) have suppressive effects on the replication of HIV in vitro. Glycyrrhizin administration was responsible 1 or improvement of immune function in 6 of 7 asymptomatic HIV carriers. Prostaglandin E2 (PGE2) and 12-0-tetradecanoylphorbol-13- acetate (TPA) were found to enhance the production of HIV significantly in infected MT-4 cells. The cell proliferation assay is used for the mass screening of neutralizing antibodies whose presence in the sera from 21 patients with AIDS, 10 individuals with ARC, 20 healthy male homosexuals and 10 healthy males was examined. The assay was sensitive enough to detect neutralizing antibodies up to a dilution of 1:10 thousand. The system using MT-4 cells seems to be suited for this purpose.
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PMID:AIDS studies in Japan. 311 53

The enhancer element of the human immunodeficiency virus type I (HIV-I) long terminal repeat (LTR) contains two copies of nearly identical sequences AGGGACTTTCC (3G sequence) and GGGGACTTTCC (4G sequence) that are important in transcriptional regulation. A single copy of the 4G sequence is found in the NF-kappa B site of the immunoglobulin kappa-chain enhancer. Only the 4G motif in the HIV enhancer is bound by cellular proteins in extracts prepared from unstimulated HeLa cells, whereas the 3G and 4G motifs are bound by factors in extracts prepared from HeLa cells treated with phorbol esters [phorbol 12-myristate 13-acetate (PMA)] and lymphoid cells. To determine if this change in binding to the HIV enhancer was due to phosphorylation of a cellular protein, partially purified PMA-treated HeLa nuclear extracts were digested with calf intestinal phosphatase. Phosphatase digestion of nuclear extracts from PMA-treated HeLa cells markedly decreased factor binding to the HIV enhancer. Accordingly, phosphorylation of the DNA binding protein itself, or an inhibitor protein present in the partially purified extract, must mediate binding to the recognition sequence. Binding studies confirmed that each of the enhancer sequences was capable of binding factors independent of the activity of the other site and that the HIV enhancer was occupied by only one factor at any one time. Chloramphenicol acetyltransferase assays using mutants in either one or both HIV enhancer repeats revealed that each site was capable of functioning as a tat-inducible enhancer element in PMA-treated HeLa cells. These results suggest that the 3G and 4G motifs in the HIV enhancer function independently and that duplication in the HIV enhancer augments activity by a mechanism distinct from cooperative binding of NF-kappa B.
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PMID:Repeated B motifs in the human immunodeficiency virus type I long terminal repeat enhancer region do not exhibit cooperative factor binding. 320 Aug 27

The effect of phorbol myristate acetate (PMA) on T4 (CD4) expression by monocytoid cells was studied. Greater than 99% of untreated U937 and HL-60 cells expressed surface T4 as measured with a fluorescence-activated cell sorter. The percentage of T4 positive cells decreased to less than 20% after incubation with PMA (10(-8) M). A decrease was observed within 15 min of PMA exposure, was maximal within 1 hr, and persisted for at least 3 days in the continuous presence of PMA. The susceptibility of untreated and PMA-treated U937 cells to human immunodeficiency virus (HIV) was also studied. Pretreatment of cells with PMA for 18 hr decreased the production of viral RNA and p24 antigen 24 hr after infection. The dose of PMA resulted in a parallel reduction of both T4 expression and infection by HIV. When PMA was washed from cultures and replaced with fresh medium for 48 hr, then T4 expression and the production viral RNA and p24 antigen following infection were restored. These data suggest that pharmacologic manipulation of surface T4 expression may have a potential role in the prevention or treatment of HIV infection.
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PMID:Rapid and reversible modulation of T4 (CD4) on monocytoid cells by phorbol myristate acetate: effect on HIV susceptibility. 336 71

The transition from persistent to lytic infection by the human immunodeficiency virus, HIV, is marked by a burst of viral replication and gene expression that occurs when infected cells are stimulated by physiological inducers or tumor promoters like 12-O-tetradecanoyl phorbol acetate (TPA). We report here that the HIV enhancer is activated specifically by TPA in several non-lymphoid cell types, and that this transcriptional regulation can be reproduced in a cell-free system. In vitro transcription experiments revealed a 6-fold activation of the HIV promoter in nuclear extracts prepared from TPA-induced HeLa tk- cells, whereas a control (human alpha-globin) promoter was transcribed with equal efficiency in either induced or uninduced cell extracts. A corresponding increase in the activity of a cellular DNA-binding protein that interacts with the HIV enhancer was detected in TPA-treated cells with DNase I footprint experiments. This increase occurred in the absence of de novo protein synthesis, suggesting a post-transcriptional activation mechanism. Analysis of HIV deletion mutants suggests that the enhancer is the target for the TPA effect both in vitro and in vivo. The cell-free system described here should facilitate studies on the mechanism of phorbol ester induction of gene-specific transcription factors.
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PMID:In vitro activation of the HIV-1 enhancer in extracts from cells treated with a phorbol ester tumor promoter. 344 2

Inherited coagulation protein deficiencies associated with bleeding diatheses may present with spontaneous bleeding early in life, or may not be recognized until the development of hemorrhage after trauma or surgery. Diagnostic evaluation with coagulation screening tests, followed by confirmation with coagulation factor assays, is essential for appropriate management. For moderate-to-severe hemophilia, treatment includes coagulation factor replacement with purified, plasma-derived coagulation factor, or in the case of hemophilia A, factor VIII concentrate produced with recombinant techniques. Increased use of pharmacologic agents such as desmopressin acetate for patients with mild hemophilia A or type 1 von Willebrand's disease has allowed physicians to treat patients without the risk of infectious complications from plasma-derived factor concentrates. In addition to the management of the inherited bleeding disorders, patients may also require management of human immunodeficiency virus infection, hepatitis, and coagulation factor inhibitors. Issues for the coming years will include continued work to ensure product safety, the role of prophylactic treatment to prevent longterm disabilities, and the application of gene therapy to the management of bleeding disorders.
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PMID:Treatment of inherited coagulation disorders. 887 17

Reducing agents such as glutathione (GSH), glutathione ester (GSE), and N-acetylcysteine (NAC) have been shown to suppress the induction of HIV expression in chronically infected cells stimulated by cytokines. We present data which show the effects of the organic thiophosphate WR-151327 on the expression of latent HIV in U1 cells. The chronically infected promonocytic cell line U1 constitutively expresses low levels of HIV that can be increased by 13-phorbol 12-myristate acetate (PMA), tumor necrosis factor alpha (TNF-alpha), and granulocyte/monocyte colony-stimulating factor (GM-CSF). WR-151327 suppressed, in dose-dependent fashion, the reverse transcriptase (RT) activity induced by TNF-alpha, GM-CSF, and PMA. The maximal decrease in RT activity was 70, 80, and 50%, respectively. Pretreatment with WR-151327 also suppressed the induction of total HIV protein synthesis, as shown by Western blot analysis. In addition, WR-151327 suppressed HIV-LTR-CAT activity in transfected human rhabdomyosarcoma cells (RD). Suppression of HIV expression by WR-151327 was observed in the absence of a cytotoxic or cytostatic effect. Incubation of WR-151327 with human recombinant TNF-alpha for 6 hr at 37 degrees C did not alter the capacity of TNF-alpha to induce the expression of HIV. Our observations further support the hypothesis that reducing agents are important in the control of HIV replication and that the clinical evaluation of WR-151327 may be indicated.
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PMID:Organic thiophosphate WR-151327 suppresses expression of HIV in chronically infected cells. 752 Nov 93

The effects of the HMG-Coenzyme A reductase inhibitor lovastatin on HIV-1 expression and sterol synthesis have been investigated in the human H9 lymphocytic cell line. To this purpose, sterol synthesis from 14C-acetate, cell multiplication and reverse transcriptase activity have been measured in parallel at various times after cell infection by HIV-1. It was found that nine days after viral loading, lovastatin inhibited both sterol synthesis and viral multiplication as assessed by the reverse transcriptase activity. Since HIV infection has been shown to induce alterations in membrane cholesterol content, suggesting that the virus cycle may be partially dependent upon cellular cholesterol, inhibitors of cholesterol synthesis could be an interesting way of research in order to slower HIV propagation.
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PMID:Lovastatin inhibits HIV-1 expression in H9 human T lymphocytes cultured in cholesterol-poor medium. 752 3

The expression of human immunodeficiency virus type 1 (HIV-1) in infected cells is induced (or enhanced) by a number of agents including phorbol myristate acetate (PMA), phytohemagglutinin (PHA), certain infectious agents, certain cytokines, and ultraviolet light. ACH2 cells represent latently HIV-1-infected T-cells, which produce only a low level of HIV-1 in vitro. We found that various anti-cancer agents including 5-azacytidine (5-AZC), 5-fluorouracil (5-FU), methotrexate, cytosine arabinoside, and vinblastine potentiated the expression of HIV-1 in ACH2 cells. There was no evidence of altered DNA methylation patterns in ACH2 cells cultured with 5-FU unlike with 5-AZC. The NF-kappa B binding activity was found to be enhanced in ACH2 cells exposed to 5-FU (but not in those exposed to 5-AZC) as assessed by the mobility shift assay using an oligonucleotide containing two NF-kappa B binding sites. These data suggest that the use of certain anti-cancer agents may induce (or enhance) the expression of HIV-1.
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PMID:HIV-1 expression induced by anti-cancer agents in latently HIV-1-infected ACH2 cells. 753 7

Aspirin [acetylsalicylic acid (ASA)], along with its analgesic-antipyretic uses, is now also being considered for cardiovascular protection and treatments in cancer and human immunodeficiency virus infection. Although many of ASA's pharmacological actions are related to its ability to inhibit prostaglandin and thromboxane biosynthesis, some of its beneficial therapeutic effects are not completely understood. Here, ASA triggered transcellular biosynthesis of a previously unrecognized class of eicosanoids during coincubations of human umbilical vein endothelial cells (HUVEC) and neutrophils [polymorphonuclear leukocytes (PMN)]. These eicosanoids were generated with ASA but not by indomethacin, salicylate, or dexamethasone. Formation was enhanced by cytokines (interleukin 1 beta) that induced the appearance of prostaglandin G/H synthase 2 (PGHS-2) but not 15-lipoxygenase, which initiates their biosynthesis from arachidonic acid in HUVEC. Costimulation of HUVEC/PMN by either thrombin plus the chemotactic peptide fMet-Leu-Phe or phorbol 12-myristate 13-acetate or ionophore A23187 leads to the production of these eicosanoids from endogenous sources. Four of these eicosanoids were also produced when PMN were exposed to 15R-HETE [(15R)-15-hydroxy-5,8,11-cis-13-trans-eicosatetraenoic acid] and an agonist. Physical methods showed that the class consists of four tetraene-containing products from arachidonic acid that proved to be 15R-epimers of lipoxins. Two of these compounds (III and IV) were potent inhibitors of leukotriene B4-mediated PMN adhesion to HUVEC, with compound IV [(5S,6R,15R)-5,6,15-trihydroxy-7,9,13-trans-11-cis-eicosatetraenoi c acid; 15-epilipoxin A4] active in the nanomolar range. These results demonstrate that ASA evokes a unique class of eicosanoids formed by acetylated PGHS-2 and 5-lipoxygenase interactions, which may contribute to the therapeutic impact of this drug. Moreover, they provide an example of a drug's ability to pirate endogenous biosynthetic mechanisms to trigger new mediators.
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PMID:Aspirin triggers previously undescribed bioactive eicosanoids by human endothelial cell-leukocyte interactions. 756 57


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