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 effects of various compounds were studied quantitatively on the growth of human immunodeficiency virus (HIV). For this we used a human T-cell leukemia virus type I carrying cell line, MT-4 which is most permissive for HIV infection. The results are summarized as follows: 1) Prostaglandin E2 and 12-0-tetradecanoylphorbol-13-acetate enhanced the production of HIV significantly in MT-4 cells as well as a continuous HIV producer Molt-4/HTLV-III cells. 2) Interferon gamma, retinoic acid and 3'-azido-3'-deoxythymidine inhibited the replication of HIV at the concentrations which were not cytotoxic. Mechanism of action of these compounds and its clinical implications are discussed.
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PMID:Substances affecting the infection and replication of human immunodeficiency virus (HIV). 303 Mar 46

T cells from human immunodeficiency virus (HIV)-infected individuals undergo spontaneous and activation-induced ex vivo apoptosis. Here we report that peripheral blood mononuclear cells (PBMCs) obtained from six HIV-infected individuals exhibited reduced ex vivo DNA fragmentation and cell death after ingestion of all-trans-retinoic acid (tRA). These effects were attenuated with continued daily RA administration, which correlated with a > 5-fold decrease in serum peak RA concentrations. Incubation of PBMCs from HIV+ individuals with tRA in vitro resulted in decreased DNA fragmentation in a subset of patients, especially those having < 500 CD4+ T cells per mm3. tRA also inhibited apoptosis of preactivated normal PBMCs induced to die by restimulation, which raises the possibility of a common mechanism between activation-induced apoptosis of activated normal PBMCs and apoptosis associated with HIV infection. Whether HIV-associated apoptosis of PBMCs, and its prevention by RA, has an impact on T-cell survival or the course of disease in patients infected with HIV will require further evaluation.
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PMID:Retinoic acid inhibition of ex vivo human immunodeficiency virus-associated apoptosis of peripheral blood cells. 770 73

Retinoids have anti-tumor activity in several malignant and premalignant conditions. Since Kaposi's sarcoma is regulated by steroid hormones both in vivo and in vitro, we hypothesized that retinoids may have anti-tumor effects in AIDS-related Kaposi's sarcoma. Thus, 27 patients with mucocutaneous, non-visceral AIDS-related Kaposi's sarcoma were treated with all-trans retinoic acid (tRA). Poor tolerance was observed at the initial starting dose of 150 mg/m2, and thus subsequent patients were treated using a weekly dose escalation, starting with 45 mg/m2 (given daily, in subdivided doses), to the target dose of 150 mg/m2 (given daily in three subdivided doses). Nearly half (46%) of the patients had extensive mucocutaneous disease with over 25 lesions. No patient had received prior cytotoxic chemotherapy. Ten patients had CD4 lymphocytes of 200/mm3 or greater (strata I); and 17 had under 200/mm3 CD4 lymphocytes (strata II). The median of the average daily tRA dose administered was 150 mg (90 mg/m2; there was no significant difference in the dose tolerance between the two strata). Adverse effects consisted of transient mild to moderate headaches in 65% of patients, mild to moderate skin dryness and cheilitis in 61%, and nausea and vomiting in 31%. Hematologic toxicities included hypertriglyceridemia in 62%, anemia in 23%, and neutropenia in 23%. Partial response to therapy was observed in 4/24 (17%) evaluable patients, occurring after 12, 20, 24, and 28 weeks of therapy, and lasting 4-24 weeks. Three responders had baseline CD4 lymphocyte counts < 200/mm3. Three additional patients experienced reduction in measured indicator lesions of greater than 25% but less than 50%, and seven patients experienced disease stabilization of 16 weeks or greater. In evaluable patients, the median time to disease progression was 22 weeks and the overall median survival in all patients was 27.3 months. No significant changes in CD4 lymphocyte counts, p24 antigen, and beta 2 microglobulin were observed over time. However, a statistically significant increase was observed in soluble IL-2 receptor levels while on tRA (p = 0.037). We conclude that tRA has activity in patients with mucocutaneous AIDS-related Kaposi's sarcoma with acceptable toxicity. tRA has immunological effects without upregulation of HIV parameters. Additional studies in combinations or with more active retinoids are warranted.
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PMID:All-trans retinoic acid for the treatment of AIDS-related Kaposi's sarcoma: results of a pilot phase II study. 780 21

Retinoids, a group of natural and synthetic vitamin A analogues the receptors of which belong to the superfamily of steroid receptors, can exert profound effects on growth and/or differentiation of embryonic and neoplastic cells. Kaposi's sarcoma (KS), previously a rare multicentric neoplasm, has become epidemic with HIV infection, although the etiology of KS remains obscure. In the present study, the effects of two potent retinoids, all-trans-retinoic acid (RA) and 13-cis-RA, on the expression of retinoic acid receptor alpha and the growth of AIDS-related KS (AIDS-KS) cells were examined. The proliferation of AIDS-KS cells was significantly inhibited by RA and 13-cis-RA in a dose-dependent manner with 50% inhibitory concentration of 1.4 x 10(-10) M and 4.7 x 10(-9) M, respectively, which correlate with their potency. Growth inhibition was time dependent with maximal inhibition of 90% after 3 days of treatment with 10(-8) M RA. Growth inhibition by RA was further potentiated by forskolin (1 microM), an intracellular cyclic AMP-inducing agent. Moreover, RA treatment blocked the proliferative effect of oncostatin M and tumor necrosis factor alpha, two major KS autocrine growth factors. The effects of RA were accompanied by a dramatic increase in nuclear staining for retinoic acid receptor alpha and in the relative number of strongly positive retinoic acid receptor alpha nuclei. Finally, RA induced morphological changes as KS cells became more flattened, better spread, and more adhesive to the substrate. These results suggest that retinoids inhibit proliferation of AIDS-KS cells and further support their utility as therapeutic agents in AIDS-KS.
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PMID:Inhibition of AIDS-Kaposi's sarcoma cell proliferation following retinoic acid receptor activation. 785 Jul 96

HL-60 cells infected with human immunodeficiency virus type 1 (HIV 1) can be induced to differentiate along the granulocyte pathway by retinoic acid. In these cells, HIV mRNA synthesis is stimulated, but synthesis of viral proteins and virus replication are blocked and HIV-infected cells die after becoming apoptotic and/or vacuolized.
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PMID:Effect of retinoic acid on HL-60 cells infected with human immunodeficiency virus type 1. 791 68

The activation of human immunodeficiency virus type 1 (HIV-1) expression in latently infected cells by exogenous agents is believed to be important in the progression of AIDS. Most factors that are known to activate HIV-1 gene expression increase the binding of NF-kappa B or NF-kappa B-like transcription factors to the HIV-1 core enhancer region. In this report, we demonstrate that retinoic acid (RA) treatment of promonocytic U937 cells stimulates expression from the simian immunodeficiency virus (SIVmac) long terminal repeat (LTR). Furthermore, RA and phorbol 12-myristate 13-acetate (PMA) synergistically stimulated both SIVmac and HIV-1 LTRs to levels of expression comparable to that achieved by the viral transactivator Tat. The cis-acting elements required for a response to RA and PMA cotreatment are located between nucleotides -50 and +1 of SIVmac and between nucleotides -83 and +80 of HIV-1. Thus, the synergistic stimulation induced by RA and PMA is NF-kappa B independent. Analysis of deletion mutants of the SIVmac LTR demonstrates that RA and PMA stimulation cooperates with NF-kappa B and Sp1. An SIVmac LTR-reporter gene construct [pLTR(-50/+466)CAT] lacking NF-kappa B and Sp1 binding sites was not activated by Tat in untreated cells but was activated in cells that were cotreated with RA and PMA. Furthermore, gel retardation assays demonstrated that RA treatment causes a change in the pattern of a cellular factor(s) which binds to the -50 through +1 region of the SIVmac LTR. These data suggest that RA induces a PMA-activatable cellular factor that cooperates with NF-kappa B, Sp1, or Tat to stimulate LTR-directed transcription.
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PMID:Synergistic activation of simian immunodeficiency virus and human immunodeficiency virus type 1 transcription by retinoic acid and phorbol ester through an NF-kappa B-independent mechanism. 808 95

We have studied human immunodeficiency virus type 1 (HIV-1) infection in human SH-SY5Y neuroblastoma cells at various stages of morphological differentiation. Two days' treatment of the cells with retinoic acid (RA) or dibutyryl cAMP (db-cAMP) resulted in the appearance of elongated neurites and enhanced production of 160K to 200K neurofilament proteins as shown by indirect immunofluorescence. DNA synthesis was reduced only in RA-treated cells as detected by 5-bromo-2'-deoxyuridine incorporation. The cells were infected with two T-lymphotropic virus strains (IIIB and NDK) and two fresh isolates (39001 and 46001) from bronchoalveolar lavage samples of AIDS patients. The latter two isolates were unable to form syncytia in infected CD4-positive T-lymphoblastoid C8166 cells which was in contrast to our T-lymphotropic virus strains. Interphase in situ hybridization showed that 14 to 16% of SH-SY5Y cells become positive for HIV-1 DNA. Regardless of the virus strain, morphological differentiation of the cells with RA or db-cAMP inhibited infection by 50% at a single cell in situ resolution. Nested PCR confirmed the presence of proviral DNA in the infected cells. These results show that human neuroblastoma cells, tumour cells of neuroectodermal origin, can be infected by different HIV-1 isolates and that the infection is inhibited by neurotypic cell differentiation.
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PMID:Morphological differentiation of human SH-SY5Y neuroblastoma cells inhibits human immunodeficiency virus type 1 infection. 811 28

A composite element that interacts with multiple nuclear receptors has been identified in the long terminal repeat (LTR) of the human immunodeficiency virus-1 (HIV-1). This element, designated nuclear receptor-responsive element (NRRE), spans the -356 to -320 LTR region and contains tightly clustered binding sites for the retinoid X receptor-alpha (RXR alpha) and for five nuclear receptors with unknown ligands, apolipoprotein AI regulatory protein-1 (ARP-1), v-erbA-related proteins-2 and -3 (EAR-2 and EAR-3), hepatocyte nuclear factor-4 (HNF-4), and nerve growth factor-inducible protein-B (NGFI-B). The NRRE also interacts with heterodimers formed between RXR alpha and either ARP-1, EAR-2, EAR-3, the retinoic acid receptor-alpha (RAR alpha), or the peroxisome proliferator-activated receptor (PPAR). Remarkably, nuclear receptor binding is conserved in the LTRs of recently evolved HIV-1 strains but it is absent in the oldest and most divergent viral isolates, raising the intriguing possibility that the NRRE has been evolved recently in the viral genome. Cotransfection experiments in human choriocarcinoma JEG-3 cells have shown that the HIV-1 LTR-driven transcription is activated by RXR alpha and RAR alpha in the presence of 9-cis- and all-trans-retinoic acid, by PPAR and RXR alpha in the presence of clofibric acid and 9-cis-retinoic acid, and by the "orphan" receptors HNF-4 and NGFI-B. These findings suggest that a complex network of nuclear receptor signaling pathways, that include 9-cis- and all-trans-retinoic acid, fatty acids, peroxisome proliferators, growth factors, membrane depolarization, and possibly other signals, converge onto the HIV-1 NRRE and may participate in modulation of viral gene expression.
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PMID:Convergence of multiple nuclear receptor signaling pathways onto the long terminal repeat of human immunodeficiency virus-1. 811 38

Retinoids regulate a broad range of biological processes and affect cell growth and differentiation of many cell types, including the immune system. Recently, it was reported that human immunodeficiency virus type 1 (HIV-1) expression in macrophages is enhanced by retinoic acid (RA). Retinoid signals are mediated by the RA receptors (RARs) and retinoid X receptors (RXRs) that bind to specific RA responsive elements (RAREs) in the promoter region of susceptible genes. Here, we report on a RARE in the long terminal repeat (LTR) region that allows activation of the HIV-1 LTR. The RARE is composed of two consensus RARE half-sites (A/GGGTCA) arranged as a palindrome separated by 9 nucleotides and is activated by both RAR/RXR heterodimers and RXR homodimers. We show that the COUP (chicken ovalbumin upstream promoter) orphan receptors also bind to the HIV-1 RARE and repress the retinoid response of the HIV-1 RARE or the HIV-1 LTR. Furthermore, a newly discovered synthetic retinoid is shown to be a potent inhibitor of retinoid-induced activation of the HIV-1 RARE. These observations suggest additional approaches for the inhibition of HIV replication.
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PMID:A synthetic retinoid antagonist inhibits the human immunodeficiency virus type 1 promoter. 820 39

The lectin jacalin is mitogenic for CD4 expressing T lymphocytes, interacts with the CD4 molecule, and inhibits HIV infection of CD4+ cells. In the present study the effect of jacalin was tested on cells from the monocyte/macrophage lineage that also express the CD4 molecule. We used CD4+ promyelomonocytic U937 cells differentiated towards the monocytic/macrophage lineage with either a mixture of two physiological agents, retinoic acid (RA) and 1 alpha,25-dihydroxyvitamin D3 (VD), or the exogenous drug phorbol myristate acetate (PMA). The cells resulting from these treatments differed in term of CD4 expression. We focused our attention on interleukin-6 (IL-6) production, which implies an activation of the cells differentiated along both pathways. In CD4+ RA/VD-treated cells, jacalin induced a 10-fold higher IL-6 secretion than did lipopolysaccharide (LPS). This jacalin-induced IL-6 production was inhibited by agents interacting with CD4 (anti-CD4 mAbs and HIV recombinant gp120) or by recombinant soluble CD4. In contrast, the CD4- PMA-differentiated U937 cells did not secrete any IL-6 upon jacalin treatment, while they demonstrated a response to LPS similar to that of the RA/VD-differentiated cells. Together with the fact that jacalin interacts with CD4, these results provide evidence of the involvement of a CD4 dependent pathway in IL-6 production.
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PMID:Involvement of CD4 in interleukin-6 secretion by U937 monocytic cells stimulated with the lectin jacalin. 830 Dec 19


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