Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:2.7.7.6 (RNA polymerase)
34,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have investigated the effects of HIV-1 infection on cellular gene expression in two different human CD4 positive lymphoid cell lines: CEM and C8166 cells. As a prerequisite for this study it was necessary to develop virus-cell culture systems in which greater than 90% of the cells could be near synchronously infected by HIV-1. Further, since HIV-1 is a cytopathic virus, it was essential that cellular gene expression be examined in virus-infected cells which remained viable. After meeting these requirements, we measured cellular RNA and protein levels in virus-infected lymphocytes. In the cell lines examined the levels of cellular protein synthesis markedly decreased at times when viral-specific protein synthesis was increasing. Both Northern and slot blot analysis revealed that the declines in host protein synthesis were due, at least in part, to declines in steady state levels of cellular mRNAs. Runoff assays with nuclei isolated from infected cells demonstrated that the decreases in cellular mRNA levels were not due to declines in cellular RNA polymerase II transcription rates. To determine if the decreases in cellular protein synthesis also might be due to specific translational controls exerted by HIV-1, we compared the polysome association of cellular RNAs in infected and uninfected C8166 cells. The polysome distribution of cellular mRNAs was virtually identical in mock- and HIV-1-infected cells although, as expected, the total amount of cellular mRNAs were significantly lower in virus-infected cells. Taken together, these results suggest that HIV-1 may encode mechanisms to inhibit cellular protein synthesis, likely as a result of cellular mRNA degradation, rather than specific blocks in cellular mRNA translation.
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PMID:Expression of cellular genes in CD4 positive lymphoid cells infected by the human immunodeficiency virus, HIV-1: evidence for a host protein synthesis shut-off induced by cellular mRNA degradation. 235 54

Viral pathogenicity may be regulated by host defense mechanisms at the virus-immune cell interaction level. The immune system plays an important role in the outcome of acute disease induced by the mouse hepatitis virus type 3 (MHV3) virus. The lymphoid cells act as effectors in the virus elimination as well as targets for viral replication. In order to demonstrate a correlation between MHV3 pathogenicity and viral replication in lymphocytes, genetically-determined resistant A/J and susceptible C57BL/6 mice were infected with pathogenic (L2-MHV3) or nonpathogenic (YAC-MHV3) viral strains. Pathogenicity and histopathologic studies have revealed that lymphoid organs such as thymus and spleen, showed injuries or atrophy in susceptible mice infected with L2-MHV3. No histopathologic lesions in the lymphoid organs occurred in C57BL/6 mice infected with YAC-MHV3 or A/J mice infected with both viruses. The mechanisms involved in the lymphoid injuries were studied regarding viral replication in the lymphoid organs and cells in infected mice. Results indicate that cell depletion in lymphoid organs is caused by a complete viral replication in lymphoid cells. Thy1.2+ and surface IgM+ lymphoid cells from susceptible C57BL/6 mice infected with L2-MHV3 were permissive to viral replication and to subsequent cell lysis. No cell lysis, however, occurred in lymphoid cells from C57BL/6 mice infected with YAC-MHV3 and A/J mice infected with both virus strains. In vitro studies, with purified T and B cell populations were performed to determine the mechanism effecting susceptibility or resistance to viral-induced cell lysis occurring in such cells. A blockade, probably occurring at the viral RNA polymerase activity level, prevents viral replication in resistant cells between the stages of fixation of the virus at the cell-surface receptor and the viral protein translation. These experiments indicate that an intrinsic virus-specific resistant mechanism occurs in lymphoid cells that plays a major role in the viral pathogenicity.
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PMID:Mouse hepatitis virus 3 replication in T and B lymphocytes correlate with viral pathogenicity. 254 12

The biosynthesis and phosphorylation of nuclear proteins of thymocytes were investigated in rats after 4.0 Gy whole-body X-irradiation during the period which precedes DNA degradation in lymphoid cells. Proteins were separated by two-dimensional gel-electrophoresis, detected by Coomassie blue staining. Incorporation of [35S]methionine into proteins and phosphorylation of proteins with [32P]inorganic phosphate were determined by scanning densitometry of autofluorograms and autoradiograms, respectively. No change in the quantity of proteins was observed 1 h after irradiation. Decrease in specific activity of [35S]methionine-labelled proteins was seen in most protein fractions. Significant enhancement of phosphorylation of three proteins was established, characterized by molecular weight and pH: MW 20 kD, pH 6.8; MW 35 kD, pH 5.8 and MW 48 kD, pH 5.8. These results suggest that immediately after X-irradiation a short-term increase of chromatin-bound non-histone protein phosphorylation occurs. This finding, along with the previously described enhancement of RNA polymerase II in thymocytes (Zhivotovsky et al. 1982) suggests a temporary gene activation shortly after X-irradiation of the rat.
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PMID:Nuclear protein synthesis in thymocytes of X-irradiated rats. 290 95

Peripheral blood lymphocytes of domestic cats were co-cultivated with lethally irradiated MT-2 cells, which produced human T-cell leukemia virus type 1 (HTLV-I). Two cat lymphoid cell lines, CaL-1 and CaL-2, established and maintained without exogenously added T-cell growth factor, were characterized after more than 6 months of cultivation. These cells grew in suspension, had a chromosome number of 38 and lacked cytoplasmic and surface immunoglobulins. CaL-2 cells formed E-rosettes. Both cell lines harbored HTLV genomes but not human Alu family sequences, which are highly repetitious in the human genome, suggesting that transfer of human DNA fragments was not necessary for their immortalization or transformation. HTLV antigens were detected in CaL-1 and CaL-2 cells by indirect immunofluorescence assay. CaL-1 and CaL-2 cells both expressed viral proteins with apparent molecular weights of 53 kd, 24 kd and 19 kd, and CaL-2 cells also expressed 28 kd and 20 kd proteins. Reverse transcriptase activity was detected in culture fluid of CaL-2 cells, but not of CaL-1 cells. CaL-2 cells but not CaL-1 cells had syncytium-induced activity. These findings indicated that lymphocytes of cats, especially T lymphocytes, were susceptible to infection with HTLV and to immortalization by HTLV.
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PMID:Immortalization of peripheral blood lymphocytes of cats by human T-cell leukemia virus. 609 83

Cytoplasmic RNA prepared from five lymphoid cell lines and a Burkitt lymphoma biopsy was radioactively labeled in vitro and hybridized to cloned EcoRI restriction endonuclease fragments of B95-8 Epstein-Barr virus DNA. The results confirmed that the most abundant cytoplasmic RNA species in such cells is specified by a small region of the genome defined by the EcoRI J fragment. Detailed mapping experiments precisely localized these transcripts within the sequence of the rightmost one-third of the EcoRI J fragment. DNA sequencing suggested that this region of the Epstein-Barr virus genome is unable to code for protein. The major early transcripts consisted of two non-polyadenylated RNA species, each about 170 nucleotides in length. They were both transcribed off the same strand of the DNA and showed significant sequence homology with each other. The coding sequences of the two small RNAs contained potential intragenic control regions for RNA polymerase III.
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PMID:Characterization of the major Epstein-Barr virus-specific RNA in Burkitt lymphoma-derived cells. 628 55

Infection of human or murine cells with murine leukemia viruses rapidly increases the expression of a number of genes that belong to the immunoglobulin superfamily and are involved in T-lymphocyte activation, including the class I major histocompatibility complex antigens. We have reported recently that the long terminal repeat (LTR) of Moloney murine leukemia virus encodes a trans activator which induces transcription and expression of class I major histocompatibility complex genes and certain cytokine genes. The portion of the LTR responsible for trans activation was mapped by deletions to lie within the U3 region. We demonstrate here that a transcript is initiated within the U3 region and that its presence correlates with the trans-activating activity. Analysis of the LTR region reveals a potential internal promoter element for RNA polymerase III transcription within the U3 region. Studies with polymerase inhibitors suggest that this LTR transcript, designated let (LTR-encoded trans activator), is a product of RNA polymerase III. The mechanisms whereby RNA leukemia viruses cause lymphoid neoplasia after a long latent period have been extensively studied but are only partially understood. The region of the LTR identified here as being important in trans activation has recently been shown to be a critical determinant of the leukemogenicity and latency of Moloney murine leukemia virus. These findings suggest a novel mechanism of retrovirus-induced activation of cellular gene expression, potentially contributing to leukemogenesis.
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PMID:A transcript from the long terminal repeats of a murine retrovirus associated with trans activation of cellular genes. 747 25

Small numbers of CD34+ primitive hematopoietic progenitors are found in normal human peripheral blood. These cells differentiate to myeloid or lymphoid lineage under the influence of different growth factors. We investigated the effects of IL5 and other growth factors on the production of eosinophils from peripheral blood CD34+ cells. CD34+ cells were enriched from normal donors by apheresis and positive selection using an affinity column and plated in agarose with different combinations of cytokines. At 14 days of growth a triple stain technique was used to identify eosinophil, monocyte, and neutrophil colonies. IL5 alone did not support colony growth from CD34+ cells. In contrast, GM-CSF and IL3 alone or together without added IL5 supported the generation of more than 50% pure eosinophil colonies. Addition of IL5 did not change the total number of colonies, but increased the fraction of pure eosinophil colonies to over 70%. Addition of G-CSF reduced the percentage of eosinophil colonies and increased the percentage of neutrophil colonies. Under the best conditions for eosinophil colony growth (IL3+GM-CSF+IL5), the addition of interferon-alpha or bacterial lipopolysaccharide inhibited colony growth by 51 and 58%, respectively. Addition of interferon-gamma, tumor necrosis factor-alpha, or dexamethasone had no effect on eosinophil colonies. Since IL5 alone did not support colony growth from CD34+ cells, we determined when IL5-responsive cells appeared in culture. Cells were grown initially with IL3 + GM-CSF in suspension, washed, and plated in agarose with IL5 alone. Only when progenitors were grown at least 3 days could IL5 serve as the single growth factor supporting pure eosinophil colony growth (47 colonies/10(4) cells plated at Day 3 and 134 colonies/10(4) cells at Day 7). We used neutralizing anti-IL5 antibodies to demonstrate that this late acting IL5 growth effect was specific, and that differentiation of eosinophils in the presence of IL3 + GM-CSF was IL5 independent. Using reverse-transcriptase polymerase chain reaction, the mRNA encoding the eosinophil-specific protein eosinophil peroxidase (EPO) was not detected in Day 0 CD34+ cells, but was demonstrated by Day 3 of culture. We conclude that within 3 days of culture, peripheral blood CD34+ cells can become committed to the eosinophil lineage as demonstrated by responsiveness to IL5 and production of EPO transcripts.
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PMID:Modulation of growth and differentiation of eosinophils from human peripheral blood CD34+ cells by IL5 and other growth factors. 753 Nov 18

Experimental autoimmune encephalomyelitis (EAE) is a T cell-mediated inflammatory demyelinating disorder of the central nervous system (CNS) which serves as a prime animal model for the human disease multiple sclerosis. Previous studies from these laboratories demonstrated excess nitric oxide (NO) in the CNS of EAE-affected mice, and amelioration of EAE with a selective inhibitor of the inducible nitric oxide synthase (iNOS). Recent studies from other laboratories have indicated that prostaglandin PGE2 is increased in CNS tissues of EAE-affected rodents and that EAE is prevented by the inhibition of cyclooxygenase activity. The present study investigated the ability of encephalitogenic lymphoid cells to induce NOS and cyclooxygenase (COX-2) in the murine macrophage line, RAW 264.7. In order to mimic the extracellular milieu present in EAE lesions, conditioned medium (CM) of activated EAE-inducer cells was added to this macrophage line. CM caused a time-dependent increase in nitrite, indicating NO production. Reverse-transcriptase PCR demonstrated iNOS mRNA in RAW 264.7 cells, first detected at 3 h, and Western blots confirmed the induction in RAW cells of the 130-kDa iNOS protein. Production of nitrite by CM-exposed RAW 264.7 cells was blocked by inhibitors of NOS (L-N-methylarginine or aminoguanidine) or by antibodies to murine IFN-gamma or IL-1 beta. CM of activated encephalitogenic cells induced production of PGE2 by RAW 264.7 cells, as determined by ELISA, and Western blots identified the presence of the 70-80-kDa inducible COX (COX-2) protein. Induction of COX-2 could be inhibited by antibody to IFN-gamma. Thus, encephalitogenic cells are capable of inducing the expression of the inflammatory enzymes iNOS and COX-2 in a murine macrophage line via the T cell cytokine IFN-gamma, alone or in combination with IL-1 beta.
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PMID:Mediation of inflammation by encephalitogenic cells: interferon gamma induction of nitric oxide synthase and cyclooxygenase 2. 759 55

A virus causing Jembrana disease in Bali cattle (Bos javanicus) was demonstrated to have characteristics of a retrovirus. Reverse transcriptase activity was detected in virus purified by sucrose gradient centrifugation. Electron microscopic examination of tissue from the affected cattle indicated that the virus matured by C-type budding through the plasma membrane and into intracytoplasmic vacuoles of cells in lymphoid tissue, with the formation of circular enveloped virus particles ranging in diameter from 96 to 124 nm with an eccentric nucleoid. Western immunoblotting using sera from recovered animals demonstrated virus proteins of M(r) 100K, 45K, 42K, 33K, 26K, 16K and 14K. The 26K protein of Jembrana disease virus cross-reacted in Western blots with the 26K capsid protein of bovine immunodeficiency virus (BIV). The apparent morphogenesis, protein structure and antigenic relationship with BIV suggested the virus was a lentivirus.
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PMID:Characteristics of a retrovirus associated with Jembrana disease in Bali cattle. 769 Aug 40

RNA polymerase II seems to be prone to stop at intrinsic pause sites, thus introducing a further potential level of regulation. It was recently shown that RNA polymerase II was held at the P2 promoter of c-myc gene. We confirmed the presence of engaged polymerases in the murine fibroblastic Ltk- and pre-B lymphoid 70Z3 cell lines. High resolution run-on analysis and in vivo permanganate-dependent footprinting showed that this holds true for the c-fos gene in unstimulated cells where a strong block to transcription elongation was evidenced. In contrast to what was observed in the c-myc gene, an even more intense signal was observed in run-on experiments downstream to the promoter, on a c-fos oligonucleotide including position +385 where an in vitro transcription arrest site was previously mapped. Genomic footprinting of DNA from intact cells and isolated nuclei confirmed the involvement of several thymidines belonging to a T-rich stretch in a melted region which was not detected upon polymerase release. In order to observe a short abortive c-fos transcript accumulating in vivo we resorted to microinjection of c-fos templates in Xenopus oocytes where transcripts were stable.
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PMID:Elongation and premature termination of transcripts initiated from c-fos and c-myc promoters show dissimilar patterns. 783 31


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