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Antiviral Genes (antiviral + gene)
Selected AbstractsToll-like receptor 3 agonist poly(I:C)-induced antiviral response in human corneal epithelial cellsIMMUNOLOGY, Issue 1 2006Ashok Kumar Summary The objective of this study was to examine the expression of Toll-like receptor 3 (TLR3) by human corneal epithelial cells (HCECs) and to determine whether exposure to the TLR3 agonist polyinosinic-polycytidylic acid [poly(I:C)]induces an antiviral response in these cells. Fluorescence-activated cell sorter (FACS) analysis revealed TLR3 to be constitutively expressed and distributed intracellularly in HCECs. Stimulation of HCECs with the TLR3 agonist poly(I:C) induced the activation of nuclear factor (NF)-,B and production of the proinflammatory cytokine interleukin (IL)-6 and the chemokine IL-8. Upon exposure to poly(I:C), HCECs initiated a potent antiviral response resulting in an increase of interferon (IFN)-, mRNA expression (7-fold). Poly(I:C) stimulation also up-regulated mRNA expression of the antiviral chemokine IFN-, inducible protein 10 (IP10), myxovirus resistance gene A and 2,,5,-oligoadenylate synthetase (5-, 10- and 9-fold, respectively), and secretion of IP10. These responses were also induced by exogenously added type 1 IFNs, but could not be blocked by pretreatment of the cells with anti-TLR3 monoclonal antibody, suggesting that the receptor was not expressed on the cell surface. Furthermore, incubation of HCECs with an endosomal acidification inhibitor, chloroquine, markedly inhibited poly(I:C)-mediated IFN-, expression in HCECs. These results suggest that corneal epithelial cells are important sentinels of the corneal innate immune system against viral infection, and that stimulation of TLR3 can induce the expression of key proinflammatory cytokines and chemokines and antiviral genes that help in the defence of the cornea against viral infection. [source] Inhibition of hepatitis B virus by lentiviral vector delivered antisense RNA and hammerhead ribozymesJOURNAL OF VIRAL HEPATITIS, Issue 4 2005K. L. Nash Summary., Chronic hepatitis B virus (HBV) infection is an important cause of cirrhosis and hepatocellular carcinoma. Current treatments are limited and may be ineffective. Nucleic acid-mediated targeting of viral mRNA is an attractive and specific approach for viral infection and lentiviral vectors provide a means to express antisense sequences or ribozymes stably in target cells permitting continuous production within that cell and its progeny. To demonstrate long-term gene expression by lentiviral vectors in hepatocytes and to introduce lentiviral vectors expressing anti-HBV genes to assess their effect against HBV, lentiviral vectors expressing a reporter gene were assessed for longevity of gene expression in hepatocytes in vitro. Hammerhead ribozymes and antisense sequences targeting the HBV encapsidation signal (,), X or surface antigen on mRNAs were cloned into lentiviral vectors and used to transduce HBV expressing hepatocytes where the effect on HBV mRNA level was assessed using ribonuclease protection. Gene expression in hepatocytes from integrated vectors continued for over 4 months without selection. Antisense RNA targeting HBs mRNA reduced this transcript, whilst antisense RNA to HBX mRNA was ineffective. Sense RNAs corresponding to , and HBX mRNA also reduced HBV mRNA levels. Ribozymes targeting HBs and HBX mRNA effectively reduced HBV mRNA levels compared with inactive constructs indicating their effect to be enzymatic rather than antisense. Lentiviral vectors can produce long-term gene expression in hepatocytes and thus permit prolonged expression of antiviral genes targeting the HBV encapsidation signal, surface and X mRNAs as treatments for chronic HBV infection. [source] Analysis of gene expression in human bronchial epithelial cells upon influenza virus infection and regulation by p38 mitogen-activated protein kinase and c-Jun-N-terminal kinaseRESPIROLOGY, Issue 2 2008Shinichi HAYASHI Background and objective: Airway epithelial cells, which are the initial site of influenza virus (IV) infection, participate in the inflammatory process through the expression of various genes. In this process, mitogen-activated protein kinase (MAPK) may be associated with the expression of many genes, but its precise role remains unknown. Methods: A comprehensive analysis was performed of gene expression in human bronchial epithelial cells upon IV infection, using an Affymetrix gene chip containing 12 000 genes. Regulation of gene expression by MAPK was also analysed. Results: A total of 5998 genes were detected. Upon IV infection, 165 genes were upregulated and 49 of these were interferon-stimulated genes. The functions of 129 genes, including 14 apoptosis-related genes and 6 antiviral genes, were well characterized; however, those of 36 genes were unknown. The expression of 29 genes was inhibited either by SB 203580, a specific inhibitor of p38 MAPK, or by CEP-11004, a specific inhibitor of the c-Jun-N-terminal kinase (JNK) cascade, and the percentage inhibition by SB 203580 correlated with that by CEP-11004, suggesting that p38 and JNK participate in a common downstream pathway involved in the regulation of gene expression. p38 MAPK- or JNK-dependent genes were functionally classified into diverse categories. Conclusions: Although further studies are needed to obtain a more complete understanding of gene expression and the role of MAPK in gene expression, the present results are important in understanding the molecular mechanisms involved in the response of bronchial epithelial cells to IV infection. [source] Antiviral gene expression in rheumatoid arthritis: Role of IKK, and interferon regulatory factor 3ARTHRITIS & RHEUMATISM, Issue 3 2007Susan E. Sweeney Objective The rheumatoid synovium displays characteristics of Toll-like receptor (TLR) activation and antiviral gene expression, including production of RANTES and interferon-, (IFN,). The mechanism of this activation in rheumatoid synovial tissue is unknown. This study was designed to investigate the role of the IKK-related kinase IKK, and IFN regulatory factor 3 (IRF-3) in the activation of antiviral genes in rheumatoid arthritis (RA). Methods Kinase assay and immunostaining were performed on synovial tissue. Dominant-negative (DN) IKK, adenoviral infection of human fibroblast-like synoviocytes (FLS) was followed by poly(I-C) stimulation and Western blotting. Quantitative polymerase chain reaction was performed on DN IKK,,infected FLS and IKK,,/, and IKK,+/+ mouse FLS. Results Western blotting showed that IKK, phosphorylation was significantly greater in RA synovium compared with osteoarthritis synovium. Kinase assay confirmed that IKK, was activated in RA synovium, and immunostaining showed localization of pIKK, to the intimal lining. Western blot analysis demonstrated that activation of IRF-3 was also increased in RA synovium. Poly(I-C), lipopolysaccharide, and tumor necrosis factor , (TNF,) activated phosphorylation of IKK, and IRF-3 in FLS. DN IKK, inhibited IRF-3 phosphorylation as well as RANTES and IFN, protein production in synoviocytes. Antiviral gene expression was also reduced in FLS from IKK,,/, mice compared with IKK,+/+ mice. Conclusion Antiviral gene expression in RA, especially due to TLR ligands and TNF,, is dependent on IKK, and IRF-3, and this pathway plays a key role in the production of type I IFNs and chemokines such as RANTES. These findings indicate that the IKK, pathway may have potential as a therapeutic target in RA. 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