DC Field | Value | Language |
---|---|---|
dc.contributor.author | Kang, Wonseok | ko |
dc.contributor.author | Sung, Pil Soo | ko |
dc.contributor.author | Park, Su-Hyung | ko |
dc.contributor.author | Yoon, Sarah | ko |
dc.contributor.author | Chang, Dong-Yeop | ko |
dc.contributor.author | Kim, Seungtaek | ko |
dc.contributor.author | Han, Kwang Hyub | ko |
dc.contributor.author | Kim, Ja Kyung | ko |
dc.contributor.author | Rehermann, Barbara | ko |
dc.contributor.author | Chwae, Yong-Joon | ko |
dc.contributor.author | Shin, Eui-Cheol | ko |
dc.date.accessioned | 2014-08-29T04:18:50Z | - |
dc.date.available | 2014-08-29T04:18:50Z | - |
dc.date.created | 2014-06-03 | - |
dc.date.created | 2014-06-03 | - |
dc.date.issued | 2014-05 | - |
dc.identifier.citation | GASTROENTEROLOGY, v.146, no.5, pp.1351 - 1360 | - |
dc.identifier.issn | 0016-5085 | - |
dc.identifier.uri | http://hdl.handle.net/10203/189050 | - |
dc.description.abstract | BACKGROUND & AIMS: Major histocompatibility complex (MHC) class I-restricted CD8(+) T cells are required for clearance of hepatitis C virus (HCV) infection. MHC class I expression is up-regulated by type I and II interferons (IFNs). However, little is known about the effects of HCV infection on IFN-induced expression of MHC class I. METHODS: We used the HCV cell culture system (HCVcc) with the genotype 2a Japanese fulminant hepatitis-1 strain to investigate IFN-induced expression of MHC class I and its regulatory mechanisms. HCVcc-infected Huh-7.5 cells were analyzed by flow cytometry, metabolic labeling, immunoprecipitation, and immunoblotting analyses. Protein kinase R (PKR) was knocked down with lentiviruses that express small hairpin RNAs. The functional effects of MHC class I regulation by HCV were demonstrated in co-culture studies, using HCV-specific CD8(+) T cells. RESULTS: Although the baseline level of MHC class I was not affected by HCV infection, IFN-induced expression of MHC class I was notably attenuated in HCV-infected cells. This was associated with replicating HCV RNA, not with viral protein. HCV infection reduced IFN-induced synthesis of MHC class I protein and induced phosphorylation of PKR and eIF2 alpha. IFN-induced MHC class I expression was restored by small hairpin RNA-mediated knockdown of PKR in HCV-infected cells. Co-culture of HCV-specific CD8(+) T cells and HCV-infected cells that expressed HLA-A2 demonstrated that HCV infection reduced the effector functions of HCV-specific CD8(+) T cells; these functions were restored by small hairpin RNA-mediated knockdown of PKR. CONCLUSIONS: IFN-induced expression of MHC class I is attenuated in HCV-infected cells by activation of PKR, which reduces the effector functions of HCV-specific CD8(+) T cells. This appears to be an important mechanism by which HCV circumvents antiviral adaptive immune responses. | - |
dc.language | English | - |
dc.publisher | W B SAUNDERS CO-ELSEVIER INC | - |
dc.subject | NATURAL-KILLER-CELLS | - |
dc.subject | PROTEIN-KINASE | - |
dc.subject | IMMUNE-RESPONSES | - |
dc.subject | ENVELOPE PROTEIN | - |
dc.subject | CORE PROTEIN | - |
dc.subject | INFECTION | - |
dc.subject | DETERMINANTS | - |
dc.subject | PERSISTENCE | - |
dc.subject | INHIBITION | - |
dc.subject | CLEARANCE | - |
dc.title | Hepatitis C Virus Attenuates Interferon-Induced Major Histocompatibility Complex Class I Expression and Decreases CD8(+) T Cell Effector Functions | - |
dc.type | Article | - |
dc.identifier.wosid | 000334507600035 | - |
dc.identifier.scopusid | 2-s2.0-84898990603 | - |
dc.type.rims | ART | - |
dc.citation.volume | 146 | - |
dc.citation.issue | 5 | - |
dc.citation.beginningpage | 1351 | - |
dc.citation.endingpage | 1360 | - |
dc.citation.publicationname | GASTROENTEROLOGY | - |
dc.identifier.doi | 10.1053/j.gastro.2014.01.054 | - |
dc.contributor.localauthor | Park, Su-Hyung | - |
dc.contributor.localauthor | Shin, Eui-Cheol | - |
dc.contributor.nonIdAuthor | Kang, Wonseok | - |
dc.contributor.nonIdAuthor | Yoon, Sarah | - |
dc.contributor.nonIdAuthor | Kim, Seungtaek | - |
dc.contributor.nonIdAuthor | Han, Kwang Hyub | - |
dc.contributor.nonIdAuthor | Kim, Ja Kyung | - |
dc.contributor.nonIdAuthor | Rehermann, Barbara | - |
dc.contributor.nonIdAuthor | Chwae, Yong-Joon | - |
dc.type.journalArticle | Article | - |
dc.subject.keywordAuthor | JFH-1 | - |
dc.subject.keywordAuthor | Antigen Presentation | - |
dc.subject.keywordAuthor | Immune Evasion | - |
dc.subject.keywordAuthor | Adaptive Immune Response | - |
dc.subject.keywordPlus | NATURAL-KILLER-CELLS | - |
dc.subject.keywordPlus | PROTEIN-KINASE | - |
dc.subject.keywordPlus | IMMUNE-RESPONSES | - |
dc.subject.keywordPlus | ENVELOPE PROTEIN | - |
dc.subject.keywordPlus | CORE PROTEIN | - |
dc.subject.keywordPlus | INFECTION | - |
dc.subject.keywordPlus | DETERMINANTS | - |
dc.subject.keywordPlus | PERSISTENCE | - |
dc.subject.keywordPlus | INHIBITION | - |
dc.subject.keywordPlus | CLEARANCE | - |
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