UMLS:C0019693 - FACTA Search

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

Human neural cells are susceptible to infection with human immunodeficiency virus type 1 (HIV-1) in vitro; however, virus replication in these cells is strongly restricted. To understand the mechanism of this restriction, we examined the regulation of HIV-1 expression in glial cell cultures expressing high levels of HIV-1 after transfection of infectious viral DNA and selection. In all cases, high HIV-1 expression declined to low basal levels within 4-8 weeks of cultivation. The decrease in HIV-1 protein production wa paralleled by the decline in the relative levels of the 9.2-, 4.3- and 1.8-kilobase HIV-1 transcripts, but not by significant loss of HIV-1 DNA. Analysis of one long-term cell culture revealed 5 full-length unrearranged HIV-1 DNA copies per cell, but no viral transcripts on Northern blots, and minimal production of infectious virus. HIV-1 replication in these cells was markedly augmented by treatment with sodium butyrate (Na But) and to a lesser extent by 5-azacytidine, dibutyryl AMP and human herpes virus type 6. The virus induced by Na But was infectious. Transient expression assays revealed that Na But was more effective than phorbol myristate acetate in increasing the HIV-1 promoter activity in glial cells. Thus, one phase where glial cells can limit HIV infection is the expression of viral RNA from stable HIV provirus. However, such provirus remains responsive to inductive signals and may be activated to produce infectious HIV.
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PMID:Regulated expression of human immunodeficiency virus type 1 in human glial cells: induction of dormant virus. 138 16

The Jurkat T cell line was stably transfected with an Epstein-Barr virus-based episomal replicon designed to express high levels of the HIV-1 Tat protein. After selection in hygromycin B, high-level Tat activity was detected in 3 of 18 transfected cell lines. After stimulation with phytohemagglutinin (PHA) and phorbol myristate acetate (PMA), Tat transfectants with high Tat expression showed diminished expression of interleukin-2 (IL-2) and the interleukin-2 receptor alpha chain (IL-2R) when compared to untransfected Jurkat cells or Jurkat cell lines transfected with the parent control plasmid. Sublines derived from the high-level Tat transfectants with reduced Tat activity showed normalization of PHA/PMA-induced IL-2 expression. Northern analysis showed diminished expression of IL-2 and IL-2R mRNA in the stimulated Tat transfectants. Inhibition of IL-2 and IL-2R expression by the HIV-1 Tat protein may contribute to the immune suppression that characterizes HIV-1 infection.
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PMID:Suppression of interleukin-2 and interleukin-2 receptor expression in Jurkat cells stably expressing the human immunodeficiency virus Tat protein. 139 41

We have isolated a lymphoid cell line, MDS, from the pleural exudate of a patient with chronic myelomonocytic leukemia. The cells are biphenotypic, containing various T-cell and myeloid markers, and are surface negative for CD4 and CD8 but have low CD4 mRNA. The cells grow in suspension with a doubling time of 15 hr, have been karyotyped as trisomy 21, are negative for human immunodeficiency virus type 1 (HIV-1), and are tumorigenic in the nude mouse. We have isolated two stable HIV-1-producing cell lines, MDS-T, by transfecting MDS cells with pHXBc2, and MDS-I, by infecting MDS cells with HIV-1IIIB. In 24 hr, 1 x 10(5) MDS-T or MDS-I cells produce 46 ng of p24 per ml and reverse transcriptase that is capable of incorporating 0.2 pmol of [32P]TTP into oligo(dT).poly(A). Ultrastructural studies showed numerous mature viral particles in MDS-T and MDS-I cells that are capable of infecting T cells. HIV-1 infection could be inhibited by 25% in the MDS cells with the anti-CD4 antibody Leu 3a. For over a year MDS-T and MDS-I cells have been producing high concentrations of HIV-1 in culture. A subclone derived from the MDS cells behaves like the parent cells when transfected or infected with HIV-1. In contrast to other T-cell lines, neither phorbol 12-myristate 13-acetate nor tumor necrosis factor alpha stimulated the replication of HIV-1, whereas bromoadenosine 3',5'-cyclic monophosphate or interferon alpha caused 50% and 80% inhibition of reverse transcriptase production, respectively. These chronically infected T-cell lines are a useful model system to study the effect of anti-HIV agents and cellular factors required for HIV-1 replication.
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PMID:Productive nonlytic human immunodeficiency virus type 1 replication in a newly established human leukemia cell line. 143 50

NF kappa B is a potent mediator of specific gene expression in human monocytes and has been shown to play a role in transcription of the HIV-1 genome in promonocytic leukemias. There is little information available on the response of NF kappa B to cytokines in normal human monocytes. We have used a 32P-labeled oligonucleotide derived from human immunodeficiency virus (HIV-1) long terminal repeat, which contains a tandem repeat of the NF kappa B binding sequence, as a probe in a gel retardation assay to study this transcription factor. Using this assay, we have detected NF kappa B in extracts of nuclei from normal human monocytes. Treatment of normal monocytes with 12-0-tetradecanoyl phorbol-13-acetate (TPA) for 4-24 h caused the complete disappearance of NF kappa B from nuclear extracts of monocytes. A similar result was obtained with the mature monocytic leukemia cell line THP-1. The constitutive transcription factor SP1 was unaffected by addition of TPA. The disappearance of NF kappa B from the nucleus was concentration dependent between 10 and 50 ng/ml of phorbol ester. In THP-1 cells, TPA also induced a new, faster-migrating NF kappa B species not induced in monocytes. Protein kinase C inhibitor staurosporine, but not cyclic nucleotide-dependent protein kinase inhibitor HA-1004, also dramatically reduced constitutive levels of nuclear NF kappa B. Finally, TPA addition to monocytes infected with HIV-1 inhibited HIV-1 replication, as determined by reverse transcriptase assays, in a concentration-dependent manner. These results are in striking contrast to the increase in nuclear NF kappa B and HIV-1 replication induced by phorbol esters in promonocytic leukemia cells U937 and HL-60, and emphasize the importance of studying cytokine regulation of HIV-1 in normal monocytes.
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PMID:Phorbol ester reduces constitutive nuclear NF kappa B and inhibits HIV-1 production in mature human monocytic cells. 146 36

Expression of HIV-1 and cytokine genes was investigated in chronically infected lymphocytic and promonocytic cell lines. As in normal human peripheral blood lymphocytes (PBL), a suboptimal activation signal with phorbol myristate acetate (PMA) did not trigger significant cytokine expression, whereas optimal activation signal (PMA + ionomycin) did. In contrast, a suboptimal activation was sufficient to up-regulate expression of HIV transcripts with kinetics similar to that observed in cells infected de novo by HIV. The level of HIV RNA in the promonocytic line was very low and markedly delayed when compared to the lymphocytic lines. We concluded that HIV induction required weaker activation signals than cytokine induction and that kinetics and level of HIV expression were not modified by induction of these cytokines. However, HIV expression appeared to alter the regulation of genes involved in proliferation and functional differentiation such as a decreased expression of IL-2 and IL-2R alpha and an increased expression of IFN gamma and TNF alpha mRNA.
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PMID:Suboptimal and optimal activation signals modulate differently the expression of HIV-1 and cytokine genes. 153 52

The nuclear factor (NF)-kappa B transcription factor system is composed of at least four inducible nucleoprotein adducts termed p50, p55 (NF-kappa B p50), p75 (NF-kappa B p65), and p85 (c-Rel). These proteins are expressed in the nuclei of activated T cells in a distinctly biphasic fashion, with p55 and p75 induction occurring within minutes whereas the induction of p50 and p85 occurs after several hours. In contrast, p50 and p55 are constitutively expressed in the nuclei of U937 and THP-1 monocytic cells. However, cellular activation is required for the nuclear expression of p75 in these cells. Additionally, activation of monocytic cells does not result in a significant induction of p85. Tumor necrosis factor alpha induces the nuclear expression of p55 and p75 in these monocytic cells within 20 min, presumably reflecting the liberation of these proteins from I kappa B. In contrast, phorbol myristate acetate (PMA) induces the expression of these proteins with delayed kinetics, raising the possibility that PMA is incapable of mediating the efficient release of p55 and p75 from I kappa B in these cells. These findings highlight important differences in the regulation of these proteins in monocytic cells versus T cells and suggest that the induced expression of NF-kappa B p65 in monocytes may play a central role in the activation of HIV-1 gene expression.
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PMID:Nuclear expression of the 50- and 65-kD Rel-related subunits of nuclear factor-kappa B is differentially regulated in human monocytic cells. 163 4

Human brain microglia may play a central role in immunopathogenesis of CNS diseases including HIV infection, multiple sclerosis and Alzheimer's disease. In order to investigate the possible relationship between microglia and the mononuclear phagocyte system, human brain microglia were isolated from 14-18-week-old fetal brains, and maintained in in vitro culture. Enriched fetal brain microglia were stained for different monocyte/macrophage and glial cell markers. Fresh dissociated brain cells lacked macrophage surface markers. Isolated microglial cells stained positive for complement receptor C3bi, Class II [human leukocyte antigen-DR (HLA-DR)] antigen and with the lectin Ricinus communis. Microglia also share several functional properties with monocyte/macrophages, which include generation of superoxide anion and histochemically demonstrable intracellular acid phosphatase and non-specific esterase. Primary human dissociated brain cultures were maintained in culture for at least 28 weeks. Although microglia were not observed above the astrocyte cell layer after 5 weeks in culture, microglia-like cells appear below the astrocyte layer after 12 weeks in culture. These cells stained positive for non-specific esterase and displayed oxidative burst activity upon activation with phorbol myristate acetate. Thus, we have successfully isolated an enriched population of microglia from human fetal brain and have demonstrated that these cells possess markers and properties which are characteristics of mononuclear phagocytes.
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PMID:Isolation and characterization of human fetal brain-derived microglia in in vitro culture. 164 2

Production of interleukin-2 (IL-2) by human T-lymphocytes can be augmented by costimulation via CD28. It has been reported that signaling via CD28 acts by stabilization of lymphokine mRNAs (Lindsten, T., June, C. H., Ledbetter, J. A., Stella, G., and Thompson, C. B. (1989) Science 244, 339-343). Here we demonstrate that costimulation via CD28 also provides a signal which activates transcription of the IL-2 gene A CD28-responsive element (CD28RE) in the IL-2 enhancer at position -162 to -152 was identified. This so far unidentified element shows sequence similarity to the kB enhancer motif. In vitro binding studies have demonstrated that the via CD28-induced signal synergizes with either phorbol myristate acetate or anti-CD3 for the induction of a nuclear factor that binds CD28RE and the human immunodeficiency virus (HIV-1) NF-kB motif. The significance of the sequence similarity of CD28RE with the kB enhancer motif was demonstrated by cross-competition studies using unlabeled CD28RE, HIV-1 NF-kB binding site, and a mutated version of the NF-kB motif. In addition, we found that NF-kB-dependent reporter gene expression was induced by costimulation via CD28. These results indicate that besides an effect on lymphokine mRNA stabilization, stimulation via CD28 acts at the level of transcription via coinduction of an NF-kB-like activity.
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PMID:Activation of interleukin-2 gene transcription via the T-cell surface molecule CD28 is mediated through an NF-kB-like response element. 165 Mar 50

The bacterial neomycin phosphotransferase gene driven by the Moloney mouse leukemia virus long terminal repeat (LTR) or SV40 early region promoter was introduced into the human promonocyte-macrophage cell line, U937, and into the pluripotential human embryonic teratocarcinoma cell line, NT2/D1. Clonally derived cell lines capable of growing in 2-4 mg/ml of the aminoglycoside antibiotic, G418 (Geneticin), were established and transfected with pHIVCat, a plasmid expressing the bacterial chloramphenicol acetyl transferase (CAT) activity under the control of the human immunodeficiency virus (HIV-1) LTR. All of the G418 resistant (neo(r)) U937 cell lines and 10 of 14 neo(r) NT2/D1 cell lines exhibited reduced basal levels of CAT expression or impaired responses to activation of the HIV-1 LTR by phorbol 12-myristate 13-acetate (PMA) when compared to the parental lines. Other differences included inhibition of tat activation of the HIV-1 LTR and increased sensitivity of U937 cells to human tumor necrosis factor alpha. The expression of other eukaryotic promoters including the HTLV-1 LTR, SV40 ori sequences, and the human beta-actin gene promoter was similarly affected. However, differentiation of the neo(r) U937 cells into macrophages was neither delayed nor impaired. Because PMA is an activator of protein kinase C (PKC) and a potent inducer of HIV-1 directed gene expression, the amounts, sensitivity to G418, and cytosol to membrane translocation of this enzyme were determined in the wild type and neo(r) U937 cells. G418 at concentrations too low to affect cell growth (12-150 micrograms/ml) inhibited PMA-induced transactivation responses in wild type cells but did not inhibit PKC-dependent protein phosphorylation in vitro. PKC activities in the wild type and neo(r) cells were similar in absolute amounts and in the cytosol-membrane distribution of the enzyme. In contrast with wild type cells, however, all of the cytosolic Ca(2+)-phospholipid-dependent form of PKC disappeared from the neo(r) cells within 30 min after PMA induction. The results suggested that, depending upon the cell type, gene cotransfer using aminoglycoside resistance as a selectable marker may seriously perturb important cellular control mechanisms such as the PKC pathway leading to activation of gene expression.
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PMID:Gene activation mediated by protein kinase C in human macrophage and teratocarcinoma cells expressing aminoglycoside phosphotransferase activity. 166 Apr 86

The antiviral effects of selected combinations between acemannan (ACE-M), a long-chained, polydispersed, beta-(1,4)-acetylated mannan, were tested in combination with azidothymidine (AZT) and acyclovir (ACY) in vitro. The rationale for such combinations was based on the antiviral and immunomodulatory properties exhibited by ACE-M. In addition, the observed antiviral effects of ACE-M against human immunodeficiency virus type 1 (HIV-1) and other enveloped viruses appear to be related to modification of the glycosylation of viral glycoproteins. Therefore, the inhibitory effect of ACE-M does not overlap with that of AZT or ACY. The studies presented herein show that ACE-M combined with suboptimal noncytotoxic concentrations of AZT or ACY act synergistically to inhibit the replication of HIV-1 and herpes simplex virus type 1 (HSV-1), respectively. The median effect method was not applicable for analysis because the test compounds show mutually nonexclusive drug effects. For a meaningful evaluation and interpretation of the effects of drug combinations, the biological significance of combinations must be considered, that is, the protective effect of the combination, the noncytotoxicity of the combination, the mechanism(s) of action of the individual compounds comprising the combination, and so forth. With respect to effects on U1 cells latently infected with HIV-1, treatment with combinations of AZT and ACE-M does not potentiate virus replication.
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PMID:In vitro evaluation of the synergistic antiviral effects of acemannan in combination with azidothymidine and acyclovir. 166 57

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