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

An important aspect of human immunodeficiency virus (HIV-1) infection is the regulation of its expression by nuclear factor kappa B (NF-kappa B) through redox-controlled signal transduction pathways. In this study, we demonstrate that iron chelation by deferoxamine (DFO) protects against the cytotoxic and reactivating effects of hydrogen peroxide (H2O2). These protective effects were observed both in lymphocytic (ACH-2) and promonocytic (U1) cells latently infected by HIV-1. Concomitantly, NF-kappa B activation by H2O2, when followed by gel retardation assay, was decreased in the DFO-treated U1 and ACH-2 cells. This latter DFO-mediated effect was specific, as DFO did not clearly affect AP-1 DNA-binding activity when studied after H2O2-induced stress. More importantly, DFO protected against the H2O2-induced activation of HIV-1 as evidenced by reverse transcriptase activity in the supernatant. DFO also protected against PMA-induced NF-kappa B activation as well as TNF-alpha-induced HIV-1 activation. Furthermore, DFO attenuated the p24 response in PBMC infected with HIV-1 and stimulated with IL-2. These different effects of DFO were obtained at DFO concentrations lower than 5 microM. Other chemically unrelated iron chelators also provided protection against cytotoxicity, NF-kappa B activation, and HIV-1 activation in U1 cells challenged with H2O2.
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PMID:Iron chelation decreases NF-kappa B and HIV type 1 activation due to oxidative stress. 855 2

IL-12 is a 70-kDa heterodimer formed by the 40-kDa heavy chain (p40) and the 35-kDa light chain (p35). Twenty-five Burkitt's lymphoma cell lines (CL) and seven normal lymphoblastoid B CL were studied. The Burkitt's CL included AIDS-associated B CL (AABCL) (7 EBV+/2 EBV-) and non-AABCL (8 EBV+/8 EBV-). Reverse transcription-PCR detected p40 in EBV+ AABCL (7 of 7), EBV+ non-AABCL (3 of 8), and normal lymphoblastoid B CL (6 of 6) but not in EBV- CL (0 of 10). p35 mRNA was detected in 30 of 30 CL. Constitutive secretion of p40 was found in 7 of 7 EBV+ AABCL (range, 341-18,086 pg/ml) and p70 in 3 of 7 EBV+ AABCL (range, 25-197 pg/ml), but in only 1 of 8 EBV+ non-AABCL and 0 of 7 normal lymphoblastoid CL. PMA stimulated p40 secretion in 7 of 7 EBV+ AABCL and p70 secretion in 5 of 7 EBV+ AABCL. PMA also triggered p40 and p70 secretion in 2 EBV+ non-AABCL and in 3 of 7 normal lymphoblastoid CL. No IL-12 secretion was detected in 10 EBV- CL, including EBV- AABCL. The CL produced IL-10, a known inhibitor of IL-12, but anti-IL-10 Abs did not neutralize IL-12. Similarly, neutralizing anti-IFN gamma Abs or IFN gamma did not affect B cell IL-12. For IL-12R studies, reverse transcription-PCR and 125I-IL-12 binding assays were performed. Although all CL tested showed mRNA accumulation for one of the IL-12R components, IL-12 binding sites were detected in only 1 of 30 CL. Our data suggest that: 1) AABCL constitutively secrete large amounts of IL-12, contrasting with low IL-12 production by HIV-1 infected PBMC; 2) lack of IL-12 expression in EBV- AABCL suggests that in vivo exposure of B cells to HIV-1 only does not induce IL-12 secretion and that both HIV-1 and EBV are required; 3) the autocrine-negative effect of IL-10 on IL-12 in monocytes and the enhancing effect of IFN gamma on IL-12 secretion do not apply to B cells derived from AIDS patients.
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PMID:IL-12 expression in AIDS-related lymphoma B cell lines. 856 69

We find that interleukin-2 (IL-2) production is severely depressed (80-90%) in AIDS T-cells (CD4+ or CD8+) stimulated with anti-CD3 or Con A together with phorbol ester (PMA) or anti-CD28 coactivation. Likewise, the proliferative response of CD4+ T-cells was suppressed, from a mean of 24.6% (HIV+) to 59.1% (AIDS) for PMA with activators OKT3 (anti-CD3), Con A, enterotoxin B or pokeweed mitogen, and 20.2% (HIV+) to 77.8% (AIDS) with anti-CD28 co-activation. Similar degrees of suppression were found with the CD8+ T-cells except for a much greater suppression at the HIV+ stage with anti-CD28 (57.7%), approximately 2.5 times higher than for PMA coactivation. However, when proliferation was induced by the two coactivators combined (PMA plus anti-CD28), much less suppression was observed: 8.5% (HIV+) to 19.0% (AIDS) for CD4+ cells and 8.2% to 26.5%, respectively, for CD8+ cells. The data suggest that during HIV infection the CD28 pathway becomes most defective, but can be bypassed to some extent by the less-impaired PMA pathway. The IL-2 (+PMA) signal in HIV+ and AIDS cells was also significantly less suppressed suggesting that the disregulation in HIV infection is more prominent prior to the IL-2 stage of the mitogenic pathway. It is remarkable that the CD4+ and CD8+ T-cells at both the HIV+ and AIDS stages generally show the same degree of suppression with all the various activators and coactivators used.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Suppressed proliferative response and interleukin-2 production in hispanic HIV+ and AIDS T-cell subsets. 857 45

Protein tyrosine kinase p59fyn (Fyn) associates with the TCR-CD3 complex, which suggests that Fyn plays a significant role in the signal transduction involving TCR complex. In addition to cellular genes, viral promoters such as the HIV long terminal repeat (LTR) are also activated upon T cell activation. To elucidate the functional significance of Fyn in the expression of viral promoters, we transfected a Fyn-expression vector together with a reporter plasmid containing the chloramphenicol acetyltransferase gene driven by HIV LTR into a human T cell line, Jurkat. In this assay, Fyn stimulated the promoter in HIV LTR when the transfected cells were treated with both concanavalin A and PMA as an antigen-mimic stimulation. This activation required the intact SH2 domain of Fyn. Mutational analysis of HIV LTR showed that the NF kappa B binding sites were responsible for this effect. Electrophoretic mobility shift assays and UV cross-linking experiments showed that activation of T cells by anti-CD3 antibody induced four kappa B-binding proteins (50, 60, 65 and 100 kDa) in Fyn-overexpressing cells more efficiently than in the parental cells. Our results suggested that Fyn was able to regulate expression of a subset of genes via kappa B-binding proteins upon T cell activation.
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PMID:The protein tyrosine kinase Fyn activates transcription from the HIV promoter via activation of NF kappa B-like DNA-binding proteins. 858 83

We had previously shown that chronically infected ACH-2 cells (HIVLAI) could be superinfected with HIVRF, that the frequency of superinfection increased with time, and that the transcription of the superinfecting virus exceeded that of the host HIVLAI provirus. In contrast, ACH-2 cells superinfected with a nef-substituted neomycin-resistant (proNEO) provirus were not detectable by DNA polymerase chain reaction (PCR) until geneticin (G418) was added, suggesting that the ability to propagate progressively in culture may be HIV strain specific. Clonal populations of ACH-2 superinfected with proNEO did not demonstrate preferential transcription of the superinfecting virus. However, clones of ACH-2 superinfected with HIVRF (ACH2/RF) showed a preponderance of HIVRF transcripts similar to that seen in bulk populations. Induction of the superinfecting virus by phorbol ester (PMA) occurred more rapidly than the hose provirus and did not equalize transcriptional activity. PCR-derived long terminal repeat (LTR) fragments and Tat cDNAs from A3.01 cells acutely infected with HIVRF or from ACH-2 cells were sequenced and tested for transactivation. The HIVLAI LTR was two to three times more Tat-responsive than the HIVRF LTR. TatRF was two to three times more transcriptionally active on either LTR than TatLAI. Demethylation with 5-azacytidine did not significantly affect HIV expression from the HIVLAI host provirus of superinfected ACH2/RF cell clones. These data suggest that the mechanism of preferential transcription in HIVRF superinfected ACH2/RF may be attributed to the Tat/TAR axis and the effect of the specific locus of host proviral integration.
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PMID:Transcriptional effects of superinfection in HIV chronically infected T cells: studies in dually infected clones. 867 41

IL-10 markedly reduces nuclear factor (NF)-kappa B/Rel nuclear activity induced in PBMC by stimulation with the anti-CD3 mAb OKT3. The inhibition is exerted specifically on the NF-kappa B/Rel activation induced by mAb OKT3, and not that produced by PMA. As judged by supershifting the DNA-protein complexes with Abs recognizing specific components of the NF-kappa B/Rel protein family, the p50/p65 (Rel A) heterodimeric form of NF-kappa B is primarily affected. The maximal effect is observed at the IL-10 concentration of 20 U/ml. IL-10 inhibitory activity is exerted on T lymphocytes and is mediated by monocytes. Indeed, monocytes pretreated with IL-10 are able so inhibit NF-kappa B nuclear activity in purified T lymphocytes stimulated with OKT3. Soluble factors do not appear to be involved in the mechanism of inhibition. On the other hand, the up-regulation of CD80 Ag, found on monocytes obtained from PBMC incubated with OKT3, is not detected after addition of IL-10, and the anti-CD28 mAb CLB-CD28/1 restores the NF-kappa B/Rel nuclear activity in IL-10-inhibited lymphocytes. Therefore, the NF-kappa B/Rel inhibition might be ascribed to a lack of cooperation between accessory cells and T lymphocytes, resulting from down-regulation of a costimulatory molecule, such as CD80, produced by IL-10 on activated monocytes. Our results demonstrate that IL-10 can inhibit the induction of NF-kappa B/Rel nuclear activity in CD3-stimulated T lymphocytes. Since inappropriate activation of kappa B-driven genes has a physiopathologic role in a number of diseases, such as HIV infection, our findings support the possibility of using this cytokine to suppress an undesirable activation of these transcription factors.
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PMID:IL-10 inhibits nuclear factor-kappa B/Rel nuclear activity in CD3-stimulated human peripheral T lymphocytes. 869 Sep

We have recently shown that ascorbic acid (AA) suppresses the production of HIV in a latently infected T-lymphocytic cell line (ACH-2) following stimulation with the tumor promoter, PMA. To evaluate the effect of ascorbic acid on virus activation following treatment with inflammatory cytokine, we tested tumor necrosis factor alpha (TNF-alpha) whose levels are elevated in patients with HIV/AIDS. ACH-2 cultures, pretreated with various nontoxic concentrations of ascorbate or AZT were stimulated for 2 h with TNF-alpha, and incubated further with fresh supplements of ascorbate or AZT. At 24 to 48 h post-treatment, the RT activity released into culture supernatant was determined. Results showed that TNF-alpha alone caused approximately 13- to 16-fold stimulation in the level of extracellular RT. Pretreatment with ascorbic acid at 200 micrograms/ml caused a little more than about 2- to 4-fold reduction in extracellular RT levels. Most remarkably, exposure to 300 micrograms/ml ascorbate resulted in approximately 5- to 10-fold lowering of the extra-cellular RT titer. In contrast, no significant suppression in extracellular RT levels was seen with concentrations of AZT in the range of 1-5 micrograms/ml.
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PMID:Ascorbate effect on cytokine stimulation of HIV production. 874 52

HIV-1 gp41 independently of CD4 binds to human T cells, B cells and monocytic cells. Since PMA downmodulates CD4 (HIV receptor) expression and inhibits HIV-1 dependent syncytia formation, we wanted to examine whether PMA could affect gp41 binding protein expression on human cells. The strong binding of HIV-1 recombinant soluble gp41 (rsgp41; Env aa539-684) to monocytes (CD14+) and B-lymphocytes (CD19+) and B lymphoblastoid cells (Raji) could be clearly decreased by treating the cells with PMA for 48 h, while the weak binding to T lymphocytes was slightly increased by this treatment. The PMA inhibitory- and enhancing-effects could be avoided by pretreatment with staurosporine (protein kinase C inhibitor). The PMA treatment of Raji and U937 (monocytic) cells resulted in a 50-60% decrease of gp41 binding proteins (gp41bps) detectable in cell lysates of these cells in comparison with lysates of buffer-treated cells, while in the case of H9-cells PMA treatment resulted in an increase of available gp41bps by about 35% in comparison with buffer-treated H9. Staurosporine pre-treatment could prevent these effects of PMA. Further studies of rsgp41-eluates from these buffer-treated or PMA-treated cells demonstrated that PMA modulated mainly expression of rsgp41bps of 37, 45, 50 and 62 kDa. These results indicate that PMA exerts different effects on human T, B and monocytic cells. Production by and expression on cells of HIV-1 gp41bps appear to depend on protein kinase C, supporting that the four proteins on human cells may act as receptor proteins for HIV-1 gp41.
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PMID:HIV-1 gp41 binding to human T- and B-lymphocytes and monocytes is modulated by phorbol myristate acetate (PMA). 880 14

MIP-1 alpha is a secreted chemokine which can inhibit hematopoietic stem cells and modulate inflammatory responses. It is also an inhibitor of HIV replication in CD8+ T-cells, MIP-1 alpha is expressed in transformed B cells and can also be induced during cellular activation of CD4+ T-cells and monocytes. We have previously identified a new transcription factor family (the MNP family) whose expression is crucial for the induction of MIP-1 alpha transcription during cellular activation. Monocytes and transformed B-cells normally express MNP-1 strongly and MNP-2 weakly, while T-cells strongly express only MNP-2. In this communication we show evidence identifying a new member of the MNP transcription family, MNP-3, in PMA differentiated HL60 cells.
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PMID:Identification of a new member of the MNP transcription factor family in differentiated HL60 cells. 880 61

Acute HIV-1 infection of H9 and C8166 cultures has been shown to be suppressed by certain flavonoids, and evidence for inhibition of HIV-1 protease, integrase, and reverse transcriptase by flavonoids also exists. The present aim was to determine whether flavonoids inhibit HIV-1 activation in models of latent infection. By screening flavonoids from six different classes, three structurally related compounds (chrysin, acacetin, and apigenin) were identified that inhibited HIV expression in TNF-alpha-treated OM-10.1 cultures. The three compounds had favorable potencies against HIV activation in relation to their growth inhibitory effects (therapeutic index 5-10). Chrysin also inhibited HIV expression in response to PMA in OM-10.1 cells, in ACH-2 cells stimulated with either TNF-alpha or PMA, and in 8E5 cultures. Furthermore, return to viral latency in OM-10.1 cells previously exposed to TNF-alpha occurred over a shorter time interval when chrysin was added. The inhibition of HIV activation was not dependent on preincubation with flavonoids relative to TNF, and was characterized by a lack of HIV RNA accumulation by Northern analysis. Gel-shift experiments revealed that NF-kappa B activation after TNF-alpha treatment was not inhibited by these agents, suggesting that some other critical factor(s) needed for viral transcription was being affected. These findings indicate that flavonoids inhibit HIV-1 activation via a novel mechanism, and that these agents are potential candidates for therapeutic strategies aimed at maintaining a cellular state of HIV-1 latency.
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PMID:Inhibition of HIV activation in latently infected cells by flavonoid compounds. 882 17


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