DC Field | Value | Language |
---|---|---|
dc.contributor.author | Sung, Pil Soo | ko |
dc.contributor.author | Cheon, HyeonJoo | ko |
dc.contributor.author | Cho, Chung Hwan | ko |
dc.contributor.author | Hong, Seon-Hui | ko |
dc.contributor.author | Park, Do Youn | ko |
dc.contributor.author | Seo, Hyung-Il | ko |
dc.contributor.author | Park, Su-Hyung | ko |
dc.contributor.author | Yoon, Seung Kew | ko |
dc.contributor.author | Stark, George R. | ko |
dc.contributor.author | Shin, Eui-Cheol | ko |
dc.date.accessioned | 2016-04-15T03:05:43Z | - |
dc.date.available | 2016-04-15T03:05:43Z | - |
dc.date.created | 2015-09-14 | - |
dc.date.created | 2015-09-14 | - |
dc.date.issued | 2015-08 | - |
dc.identifier.citation | PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, v.112, no.33, pp.10443 - 10448 | - |
dc.identifier.issn | 0027-8424 | - |
dc.identifier.uri | http://hdl.handle.net/10203/203958 | - |
dc.description.abstract | Up-regulation of IFN-stimulated genes (ISGs) is sustained in hepatitis C virus (HCV)-infected livers. Here, we investigated the mechanism of prolonged ISG expression and its role in IFN responsiveness during HCV infection in relation to unphosphorylated IFN-stimulated gene factor 3 (U-ISGF3), recently identified as a tripartite transcription factor formed by high levels of IFN response factor 9 (IRF9), STAT1, and STAT2 without tyrosine phosphorylation of the STATs. The level of U-ISGF3, but not tyrosine phosphorylated STAT1, is significantly elevated in response to IFN-lambda and IFN-beta during chronic HCV infection. U-ISGF3 prolongs the expression of a subset of ISGs and restricts HCV chronic replication. However, paradoxically, high levels of U-ISGF3 also confer unresponsiveness to IFN-alpha therapy. As a mechanism of U-ISGF3-induced resistance to IFN-alpha, we found that ISG15, a U-ISGF3-induced protein, sustains the abundance of ubiquitin-specific protease 18 (USP18), a negative regulator of IFN signaling. Our data demonstrate that U-ISGF3 induced by IFN-lambda s and -beta drives prolonged expression of a set of ISGs, leading to chronic activation of innate responses and conferring a lack of response to IFN-alpha in HCV-infected liver. | - |
dc.language | English | - |
dc.publisher | NATL ACAD SCIENCES | - |
dc.subject | HEPATITIS-C VIRUS | - |
dc.subject | INNATE IMMUNE-RESPONSE | - |
dc.subject | GENE-EXPRESSION | - |
dc.subject | STIMULATED GENES | - |
dc.subject | ALPHA-INTERFERON | - |
dc.subject | INTERLEUKIN 28B | - |
dc.subject | CELLS | - |
dc.subject | HEPATOCYTES | - |
dc.subject | LIVER | - |
dc.subject | STAT1 | - |
dc.title | Roles of unphosphorylated ISGF3 in HCV infection and interferon responsiveness | - |
dc.type | Article | - |
dc.identifier.wosid | 000359738300081 | - |
dc.identifier.scopusid | 2-s2.0-84939823954 | - |
dc.type.rims | ART | - |
dc.citation.volume | 112 | - |
dc.citation.issue | 33 | - |
dc.citation.beginningpage | 10443 | - |
dc.citation.endingpage | 10448 | - |
dc.citation.publicationname | PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | - |
dc.identifier.doi | 10.1073/pnas.1513341112 | - |
dc.contributor.localauthor | Park, Su-Hyung | - |
dc.contributor.localauthor | Shin, Eui-Cheol | - |
dc.contributor.nonIdAuthor | Cheon, HyeonJoo | - |
dc.contributor.nonIdAuthor | Hong, Seon-Hui | - |
dc.contributor.nonIdAuthor | Park, Do Youn | - |
dc.contributor.nonIdAuthor | Seo, Hyung-Il | - |
dc.contributor.nonIdAuthor | Yoon, Seung Kew | - |
dc.contributor.nonIdAuthor | Stark, George R. | - |
dc.type.journalArticle | Article | - |
dc.subject.keywordAuthor | hepatitis C virus | - |
dc.subject.keywordAuthor | U-ISGF3 | - |
dc.subject.keywordAuthor | interferon | - |
dc.subject.keywordAuthor | interferon-stimulated genes | - |
dc.subject.keywordPlus | HEPATITIS-C VIRUS | - |
dc.subject.keywordPlus | INNATE IMMUNE-RESPONSE | - |
dc.subject.keywordPlus | GENE-EXPRESSION | - |
dc.subject.keywordPlus | STIMULATED GENES | - |
dc.subject.keywordPlus | ALPHA-INTERFERON | - |
dc.subject.keywordPlus | INTERLEUKIN 28B | - |
dc.subject.keywordPlus | CELLS | - |
dc.subject.keywordPlus | HEPATOCYTES | - |
dc.subject.keywordPlus | LIVER | - |
dc.subject.keywordPlus | STAT1 | - |
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