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)

A palindromic element (site B) located between bases -328 and -347 (relative to the start site of transcription) of the human immunodeficiency virus type 1 (HIV-1) long terminal repeat (LTR) was shown in a gel mobility shift assay to bind the human retinoic acid receptors (RARs). Greatly enhanced binding to this site was observed in the presence of both RAR and the retinoid X receptor. Retinoic acid responsiveness in F9 cells could be conferred on a thymidine kinase promoter by the presence of single or multiple copies of site B and responsiveness was abolished when this sequence was mutated to a form that could not bind RARs. However, the presence of this sequence did not render the HIV-1 LTR responsive to retinoic acid in F9 cells.
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PMID:A palindromic element in the human immunodeficiency virus long terminal repeat binds retinoic acid receptors and can confer retinoic acid responsiveness on a heterologous promoter. 838 9

As a model system to study the infection of early myeloid cells by human immunodeficiency virus-1 (HIV-1), we have infected the human promyelocytic cell line, HL-60, with a recombinant selectable HIV-1 clone. A fully infected population showed a relatively high frequency of low-level infection, with 40% of subcloned cells being negative by reverse transcriptase and p24 indirect immunofluorescence analysis and displaying only low levels of supernatant p24. The same treatment of a T-lymphoid cell line produced 100% productive infections. HIV-1 infection of HL-60 did not appear to alter the state of differentiation of the cells, as assessed by surface antigen expression, regardless of the level of viral expression. Furthermore, infected cells were able to respond normally to chemical inducers of differentiation. Induction of differentiation towards monocyte/macrophages by phorbol myristate acetate activated the HIV-1 long terminal repeat in a transient transfection system, and there was a corresponding increase in viral production from the infected subclones. Granulocytic differentiation, as stimulated by dimethyl sulfoxide or retinoic acid, had no effect on long terminal repeat activity and did not stimulate viral replication. These data suggest that low-level HIV-1 infections may be established at a relatively high frequency in myeloid precursor cells, and that different pathways of promyelocytic differentiation vary in their ability to stimulate HIV-1 replication.
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PMID:Human immunodeficiency virus-1 infection of the human promyelocytic cell line HL-60: high frequency of low-level infection and effect of subsequent cell differentiation. 842 63

Fluid shear stress activates the expression of immediate early (IE) genes in vascular endothelial cells. The transcriptional regulation can be mediated through the shear stress-sensitive cis-acting elements at the 5' promoter regions of various IE genes such as the monocyte chemotactic protein-1 (MCP-1) gene. We linked wild-type and mutated MCP-1 promoters to the reporter gene luciferase and used such constructs to investigate the role of the phorbol ester TPA responsive element (TRE) in the shear-induced MCP-1 gene expression in vascular endothelial cells. Functional analysis showed that TGACTCC (a divergent TRE) located at nt -54 to -60 is necessary for shear-inducibility in bovine aortic endothelial cells (BAEC). The induction of the wild-type MCP-1 promoter construct by shear stress was attenuated by pretreating the cells with 1 microM dexamethasone or 1 microM retinoic acid 12 h before the shear stress experiments. The induction by shear stress reduced from 13-fold in the untreated cells to 7- and 3-folds in the dexamethasone- and retinoic acid-treated cells, respectively. These results demonstrate that the glucocorticoid receptor and retinoic acid receptor may interfere with the shear stress-activated AP-1/TRE. The reporter activity of HIV(LTR), which is a plasmid construct of the long terminal repeats of the human immunodeficiency virus and contains a kappa B enhancer element, was also activated by shear stress. The results of our investigations indicate that the shear stress-induced IE gene expression can be mediated through multiple cis-elements.
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PMID:Multiple cis-elements mediate shear stress-induced gene expression. 866 85

Infection of cells of the central nervous system by the human immunodeficiency virus type-1 (HIV-1) leads to HIV-1-associated neuropathology. Recent studies have demonstrated the importance of long terminal repeat (LTR) binding sites in determining the pathogenicity of HIV. Here we have investigated the presence and the functional role of transcription factors that have the potential to interact, directly or indirectly, with the nuclear receptor-responsive element in the LTR of HIV-1, in different human cell lines of the brain. Cotransfection experiments showed that in oligodendroglioma TC-620 cells, the retinoic acid receptor and the retinoid X receptor activate LTR-driven transcription in the absence of ligand. Addition of all-trans- or 9-cis-retinoic acid reverses this effect. In contrast, in astrocytoma, neuronal, and microglial cells, no significant effect of the retinoid acid pathway was detected. This retinoid response is mediated by distinct molecular interactions in the lymphotropic LAI and the neurotropic JR-CSF HIV-1 strains. Moreover, retinoid receptors were found to antagonize the chicken ovalbumin upstream promoter transcription factor- as well as the c-JUN-mediated LTR transactivation. Our findings demonstrate the importance of the retinoic acid signaling pathway and of cross-coupling interactions in the repression of HIV-1 LTR gene expression.
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PMID:Regulation of human immunodeficiency virus type 1 gene transcription by nuclear receptors in human brain cells. 879 69

We have used a panel of anti-gp160 MAbs to construct anti-HIV immunotoxins by coupling antibodies to ricin A chain (RAC). The ability of the immunotoxins to kill HIV-1-infected cells and halt the spread of infection was tested in tissue culture on persistently and acutely infected cell lines and primary lymphocyte cultures stimulated with phytohemagglutinin (PHA blasts). Laboratory strains and clinical isolates of HIV both were tested. The constitution and antigen-binding capacity of the immunotoxins were confirmed by ELISA and indirect immunofluorescence. Immunotoxins that bind epitopes exposed on the cell surface effectively killed persistently infected cells, although killing was not directly proportional to binding of immunotoxin to cell. The activity of anti-gp41, but not anti-gp120, immunotoxins was markedly enhanced in the presence of soluble CD4 or peptides corresponding to the CDR3 region of CD4. CD4-mediated enhancement of anti-gp41 immunotoxin activity was observed for laboratory strains neutralized by sCD4 and for clinical isolates that were resistant to neutralization by sCD4. Immunotoxin action was potentiated by brefeldin A, bafilomycin A1, cortisone, and an amphipathic fusion peptide, but not by cytochalasin D, nocodazol, monodansyl cadaverine, or trans-retinoic acid. Anti-HIV immunotoxins are useful tool with which to study the functional expression of gp120/gp41 antigens on the surface of HIV-infected cells, as well as potential AIDS therapeutics. Because these studies relate to the accessibility of viral antigens to antibody-mediated attack, these studies also have relevance for vaccine development.
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PMID:In vitro effects of anti-HIV immunotoxins directed against multiple epitopes on HIV type 1 envelope glycoprotein 160. 882 20

We employed a recombinant plasmid, pBHIV1, carrying the long terminal repeat (LTR) sequences of HIV-1 linked to the reporter chloramphenicol acetyl transferase (CAT) gene and to the aminoglycoside phosphotransferase (aph) gene as a selectable marker. We introduced pBHIV1 into human epithelial and fibroblast tumor cell lines (HeLa and MRCSV40TGR), and obtained stable geneticin-resistant HLHIV1-A and SVTGHIV1-A cells, respectively. The response to the retinoic acid was studied on the LTR regulated CAT activity in both cell lines. It was found that retinoic acid at a concentration of 1x10(-5) effects a 3.2 -fold increase in CAT expression compared to HIV LTR in HLHIV1-A, but requires a concentration of 5x10(-5) M to enhance this expression 4.6-fold in SVTGHIV1-A cells. These data show that retinoic acid may play a critical role in HIV-1 expression in human epithelial and fibroblast cell lines.
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PMID:Transcriptional activation of the human immunodeficiency virus long terminal repeat sequences by retinoic acid in human epithelial and fibroblast tumor cell lines. 891 10

In recent years, new physiological functions of vitamin A have been identified in addition to its role in vision, namely its role in immune defence reducing morbidity of measles, of respiratory and possibly HIV infections, in gene regulation, in cell differentiation and morphogenesis. With the discovery of nuclear receptors for retinoic acid additional functions are likely to be found. The recommended dietary allowances (RDA) for vitamin A, including provitamin A carotenoids, vary greatly between countries. This may be explained by difficulties in establishing needs: Homeostatic mechanisms tightly control absorption, storage, release and transport of vitamin A to target tissue, and plasma concentrations do not reflect status unless there is vitamin A deficiency or excess. In the United States RDAs were established on the basis of vitamin A depletion-repletion studies with radio-labelled retinol. Intake requirements were calculated to amount to 1,000 micrograms retinol equivalents (RE) for men, 800 micrograms RE for non-pregnant as well as pregnant women and 1,300 micrograms RE for lactating women. Dietary intake studies in different countries have shown that it is in principle possible to obtain these values from the diet either as preformed vitamin A or in the form of provitamin A carotenoids or both. Risk groups for inadequate intakes include low-income groups and younger persons following weight-reducing and other unbalanced diets. Since experience with recommended intake values in the United States has been excellent, attempts at reducing these levels are unjustified and should be resisted. At intakes of up to three RDA values (approximately 3,000 micrograms RE) no unwanted side-effects are to be expected. Even higher doses, if not taken chronically, have been well tolerated, e.g. in deprived populations with low liver reserves. The suggestion derived from a case-control study that vitamin A taken at supplemental doses of 2,400 micrograms RE may be teratogenic have not been confirmed by several other studies. But it is judicious to follow the recommendations of the American Pediatric Society that women should not exceed a total daily intake of 3,000 micrograms RE. In developing countries where acute and chronic vitamin A deficiency is endemic causing xerophthalmia and blindness and increasing the prevalence of infectious diseases and death in children, special efforts are being made by WHO/UNICEF to provide programs for the eradication of vitamin A deficiency by immediate treatment and by long-term changes in dietary practices.
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PMID:Vitamin A--functions, dietary requirements and safety in humans. 912 49

Fifteen men with HIV-associated Kaposi's sarcoma (KS) and poor risk disease according to the TIS staging were enrolled in a phase II trial of oral 13-cis-retinoic acid. The median CD4 cell count was 95 cells/microl (range 7-260) and 6 had prior AIDS-defining opportunistic infections. One patient was withdrawn on account of cutaneous toxicity. Evaluation was by AIDS Clinical Trials Group (ACTG)1 defined assessment. One patient achieved a partial response and remains on treatment in partial remission. Thus the overall response rate is 7% (95% confidence interval 0-23%). A further 5 patients had stable disease (38%: 95% confidence interval 7-64%). The overall low activity, considerable toxicity and limited cosmetic benefit even in responding patients limits the value of this approach in KS. However, this treatment strategy may be more rewarding in early good risk KS.
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PMID:Phase II trial of 13-cis-retinoic acid for poor risk HIV-associated Kaposi's sarcoma. 925 1

Retinoids have been shown to modulate cell growth and differentiation in a variety of human tumor cell types, but their effects on B-cell non-Hodgkin's lymphomas (NHL-B) have not been explored. In this study, all-trans retinoic acid (ATRA) in the free form and liposome-encapsulated form (L-ATRA) were used to determine effects on fresh NHL-B patient cells as well as cell lines recently established from both HIV-negative and -positive NHL-B patient biopsies. Both ATRA and L-ATRA were found to inhibit cell proliferation in NHL-B cells. However, L-ATRA was found to be superior to free ATRA in inhibiting cell proliferation of NHL-B cells and resulted in greater than 90% cell growth inhibition in a dose-dependent manner. In addition, L-ATRA also induced high levels of apoptosis in NHL-B cells in vitro. To delineate the apoptotic pathways involved, the expression of the apoptosis suppressor oncogene bcl-2 was evaluated in different NHL-B cells with and without the t(14;18) chromosomal translocation. After L-ATRA exposure, more than a 50% reduction in the expression of bcl-2 protein was observed. bcl-2 message levels were also down-regulated in the L-ATRA-sensitive NHL-B cells. Bax protein levels were analyzed and found to be up-regulated in L-ATRA-sensitive NHL-B cells. Similar results were observed in sensitive AIDS/lymphoma cell lines. Experiments using an RAR-alpha antagonist (RO 41-5253) showed that both the proliferation inhibition and apoptosis induced by L-ATRA could be blocked in NHL-B cells. The findings of the present study indicate that L-ATRA may possess therapeutic potential in blocking cell proliferation, inducing apoptosis, and
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PMID:Retinoid-mediated inhibition of cell growth with stimulation of apoptosis in aggressive B-cell lymphomas. 934 85

Acute myeloid leukemia (AML) is infrequent in patients with human immunodeficiency virus (HIV) infection. Among AML, acute promyelocytic leukemia (APL) has been rarely described in such patients, with only one case being published. We report a 30 years-old intravenous drug abuser HIV-infected male with APL who attained complete clinical, morphological, and molecular remission after differentiation therapy with all-trans-retinoic acid (ATRA) followed by intensive chemotherapy. The results of treatment in this patient and in other AML published cases suggest that therapy for AML should not be modified because of HIV infection if patients have an adequate performance status.
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PMID:Acute promyelocytic leukemia in a HIV seropositive patient. 938 70


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