DC Field | Value | Language |
---|---|---|
dc.contributor.author | Sung, Pil Soo | ko |
dc.contributor.author | Hong, Seon-Hui | ko |
dc.contributor.author | Chung, Jae-Hee | ko |
dc.contributor.author | Kim, Sojeong | ko |
dc.contributor.author | Park, Su-Hyung | ko |
dc.contributor.author | Kim, Ho Min | ko |
dc.contributor.author | Yoon, Seung Kew | ko |
dc.contributor.author | Shin, Eui-Cheol | ko |
dc.date.accessioned | 2017-11-06T09:02:51Z | - |
dc.date.available | 2017-11-06T09:02:51Z | - |
dc.date.created | 2017-08-02 | - |
dc.date.created | 2017-08-02 | - |
dc.date.issued | 2017-06 | - |
dc.identifier.citation | SCIENTIFIC REPORTS, v.7 | - |
dc.identifier.issn | 2045-2322 | - |
dc.identifier.uri | http://hdl.handle.net/10203/226674 | - |
dc.description.abstract | Genetic polymorphisms in IFNL4 have been shown to predict responses to IFN-alpha-based therapy in hepatitis C virus (HCV)-infected patients. The IFNL4-Delta G genotype, which encodes functional IFN-lambda 4 protein, is associated with a poor treatment response. In the present study, we investigated the induction and biological effects of IFN-lambda 4 in HCV-infected hepatocytes and their association with responsiveness to IFN-alpha. We also studied the effects of direct-acting antiviral (DAA) treatment on IFN-lambda 4 expression and IFN-alpha responsiveness. HCV infection induced IFN-lambda 4 expression at mRNA and protein levels in primary human hepatocytes (PHHs). In hepatoma cells, IFNL4 gene transfection or recombinant IFN-lambda 4 protein treatment robustly increased the protein levels of ISG15 and USP18 in an IFNLR1-dependent manner and potently blocked IFN-alpha signalling. The ISG15/USP18-mediated IFN-alpha unresponsiveness was demonstrated by transfection of siRNAs targeting ISG15 and/or USP18. This potent IFN-lambda 4 effect was related to prolonged ISG expression after IFNL4 gene transfection. DAA treatment of HCV-infected PHHs reduced the expression of IFN-lambda s, including IFN-lambda 4, and restored IFN-alpha responsiveness. These results demonstrate that virus-induced IFN-lambda 4 potently blocks IFN-alpha signalling by inducing high protein levels of ISG15 and USP18. Moreover, the data clearly demonstrate that DAA therapy restores IFN-alpha responsiveness in HCV-infected cells. | - |
dc.language | English | - |
dc.publisher | NATURE PUBLISHING GROUP | - |
dc.subject | INTERFERON-STIMULATED GENES | - |
dc.subject | INNATE IMMUNE-RESPONSE | - |
dc.subject | HCV INFECTION | - |
dc.subject | LAMBDA 4 | - |
dc.subject | CLEARANCE | - |
dc.subject | CELLS | - |
dc.subject | EXPRESSION | - |
dc.subject | IL28B | - |
dc.subject | ASSOCIATION | - |
dc.title | IFN-lambda 4 potently blocks IFN-alpha signalling by ISG15 and USP18 in hepatitis C virus infection | - |
dc.type | Article | - |
dc.identifier.wosid | 000403650300064 | - |
dc.identifier.scopusid | 2-s2.0-85021094566 | - |
dc.type.rims | ART | - |
dc.citation.volume | 7 | - |
dc.citation.publicationname | SCIENTIFIC REPORTS | - |
dc.identifier.doi | 10.1038/s41598-017-04186-7 | - |
dc.contributor.localauthor | Park, Su-Hyung | - |
dc.contributor.localauthor | Kim, Ho Min | - |
dc.contributor.localauthor | Shin, Eui-Cheol | - |
dc.contributor.nonIdAuthor | Yoon, Seung Kew | - |
dc.description.isOpenAccess | Y | - |
dc.type.journalArticle | Article | - |
dc.subject.keywordPlus | INTERFERON-STIMULATED GENES | - |
dc.subject.keywordPlus | INNATE IMMUNE-RESPONSE | - |
dc.subject.keywordPlus | HCV INFECTION | - |
dc.subject.keywordPlus | LAMBDA 4 | - |
dc.subject.keywordPlus | CLEARANCE | - |
dc.subject.keywordPlus | CELLS | - |
dc.subject.keywordPlus | EXPRESSION | - |
dc.subject.keywordPlus | IL28B | - |
dc.subject.keywordPlus | ASSOCIATION | - |
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.