6 268

Cited 20 times in

Hepatitis C Virus Attenuates Interferon-Induced Major Histocompatibility Complex Class I Expression and Decreases CD8+ T Cell Effector Functions

DC FieldValueLanguage
dc.contributor.author강원석-
dc.contributor.author김승택-
dc.contributor.author김자경-
dc.contributor.author한광협-
dc.date.accessioned2015-01-06T16:58:28Z-
dc.date.available2015-01-06T16:58:28Z-
dc.date.issued2014-
dc.identifier.issn0016-5085-
dc.identifier.urihttps://ir.ymlib.yonsei.ac.kr/handle/22282913/99129-
dc.description.abstractBACKGROUND & 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 eIF2α. 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.description.statementOfResponsibilityopen-
dc.format.extent1351~1360-
dc.relation.isPartOfGASTROENTEROLOGY-
dc.rightsCC BY-NC-ND 2.0 KR-
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/2.0/kr/-
dc.subject.MESHAdaptive Immunity*-
dc.subject.MESHCD8-Positive T-Lymphocytes/immunology*-
dc.subject.MESHCD8-Positive T-Lymphocytes/metabolism-
dc.subject.MESHCD8-Positive T-Lymphocytes/virology-
dc.subject.MESHCell Line, Tumor-
dc.subject.MESHCoculture Techniques-
dc.subject.MESHDNA Replication-
dc.subject.MESHDNA, Viral/biosynthesis-
dc.subject.MESHDown-Regulation-
dc.subject.MESHEnzyme Activation-
dc.subject.MESHEukaryotic Initiation Factor-2/metabolism-
dc.subject.MESHGenotype-
dc.subject.MESHHepacivirus/genetics-
dc.subject.MESHHepacivirus/growth & development-
dc.subject.MESHHepacivirus/immunology*-
dc.subject.MESHHepacivirus/metabolism-
dc.subject.MESHHepacivirus/pathogenicity-
dc.subject.MESHHepatocytes/immunology*-
dc.subject.MESHHepatocytes/metabolism-
dc.subject.MESHHepatocytes/virology-
dc.subject.MESHHistocompatibility Antigens Class I/genetics-
dc.subject.MESHHistocompatibility Antigens Class I/metabolism*-
dc.subject.MESHHost-Pathogen Interactions-
dc.subject.MESHHumans-
dc.subject.MESHInterferons/metabolism*-
dc.subject.MESHPhosphorylation-
dc.subject.MESHRNA Interference-
dc.subject.MESHSignal Transduction-
dc.subject.MESHTransfection-
dc.subject.MESHeIF-2 Kinase/genetics-
dc.subject.MESHeIF-2 Kinase/metabolism-
dc.titleHepatitis C Virus Attenuates Interferon-Induced Major Histocompatibility Complex Class I Expression and Decreases CD8+ T Cell Effector Functions-
dc.typeArticle-
dc.contributor.collegeCollege of Medicine (의과대학)-
dc.contributor.departmentDept. of Life Science (의생명과학부)-
dc.contributor.googleauthorWonseok Kang-
dc.contributor.googleauthorPil Soo Sung-
dc.contributor.googleauthorSu-Hyung Park-
dc.contributor.googleauthorSarah Yoon-
dc.contributor.googleauthorDong-Yeop Chang-
dc.contributor.googleauthorSeungtaek Kim-
dc.contributor.googleauthorKwang Hyub Han-
dc.contributor.googleauthorJa Kyung Kim-
dc.contributor.googleauthorBarbara Rehermann-
dc.contributor.googleauthorYong-Joon Chwae-
dc.contributor.googleauthorEui-Cheol Shin-
dc.identifier.doi10.1053/j.gastro.2014.01.054-
dc.admin.authorfalse-
dc.admin.mappingfalse-
dc.contributor.localIdA00061-
dc.contributor.localIdA00661-
dc.contributor.localIdA00852-
dc.contributor.localIdA04268-
dc.relation.journalcodeJ00917-
dc.identifier.eissn1528-0012-
dc.identifier.pmid24486950-
dc.identifier.urlhttp://www.sciencedirect.com/science/article/pii/S0016508514001450-
dc.subject.keywordAdaptive Immune Response-
dc.subject.keywordAntigen Presentation-
dc.subject.keywordImmune Evasion-
dc.subject.keywordJFH-1-
dc.contributor.alternativeNameKang, Won Suk-
dc.contributor.alternativeNameKim, Seung Taek-
dc.contributor.alternativeNameKim, Ja Kyung-
dc.contributor.alternativeNameHan, Kwang Hyup-
dc.contributor.affiliatedAuthorKang, Won Suk-
dc.contributor.affiliatedAuthorKim, Seung Taek-
dc.contributor.affiliatedAuthorKim, Ja Kyung-
dc.contributor.affiliatedAuthorHan, Kwang Hyup-
dc.rights.accessRightsfree-
dc.citation.volume146-
dc.citation.number5-
dc.citation.startPage1351-
dc.citation.endPage1360-
dc.identifier.bibliographicCitationGASTROENTEROLOGY, Vol.146(5) : 1351-1360, 2014-
Appears in Collections:
1. College of Medicine (의과대학) > BioMedical Science Institute (의생명과학부) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers

qrcode

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.