202 373

Cited 4 times in

Hepatitis C virus impairs natural killer cell activity via viral serine protease NS3

DC Field Value Language
dc.contributor.author박전한-
dc.contributor.author이재면-
dc.date.accessioned2017-11-02T08:32:00Z-
dc.date.available2017-11-02T08:32:00Z-
dc.date.issued2017-
dc.identifier.urihttps://ir.ymlib.yonsei.ac.kr/handle/22282913/154572-
dc.description.abstractHepatitis C virus (HCV) infection is characterized by a high frequency of chronic cases owing to the impairment of innate and adaptive immune responses. The modulation of natural killer (NK) cell functions by HCV leads to an impaired innate immune response. However, the underling mechanisms and roles of HCV proteins in this immune evasion are controversial, especially in the early phase of HCV infection. To investigate the role of HCV nonstructural proteins especially NS3 in the impairment of NK functions, NK cells were isolated from the PBMCs by negative selection. To assess the direct cytotoxicity and IFN-γ production capability of NK cells, co-cultured with uninfected, HCV-infected, HCV-NS3 DNA-transfected Huh-7.5, or HCV-NS replicon cells. To determine the effect of an NS3 serine protease inhibitor, HCV-infected Huh-7.5 cells were treated with BILN-2061. Then, NK cells were harvested and further co-cultured with K-562 target cells. NK cell functions were analyzed by flow cytometry and enzyme-linked immunosorbent assay. When co-cultured with HCV-infected Huh-7.5 cells, the natural cytotoxicity and IFN-γ production capability of NK cells were significantly reduced. NK cell functions were inhibited to similar levels upon co-culture with HCV-NS replicon cells, NS3-transfected cells, and HCV-infected Huh-7.5 cells. These reductions were restored by BILN-2061-treatment. Furthermore, BILN-2061-treatment significantly increased degranulation against K-562 target cells and IFN-γ productivity in NK cells. Consistent with these findings, the expression levels of activating NK cell receptors, such as NKp46 and NKp30, were also increased. In HCV-infected cells, the serine protease NS3 may play a role in the abrogation of NK cell functions in the early phase of infection through downregulation of NKp46 and NKp30 receptors on NK cells. Together, these results suggest that NS3 represents a novel drug target for the treatment of HCV infections.-
dc.description.statementOfResponsibilityopen-
dc.languageEnglish-
dc.publisherPublic Library of Science-
dc.relation.isPartOfPLOS ONE-
dc.rightsCC BY-NC-ND 2.0 KR-
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/2.0/kr/-
dc.subject.MESHCarbamates/chemistry-
dc.subject.MESHCarbamates/pharmacology-
dc.subject.MESHCell Line-
dc.subject.MESHCell Survival/drug effects-
dc.subject.MESHCoculture Techniques-
dc.subject.MESHDown-Regulation/drug effects-
dc.subject.MESHHepacivirus/enzymology*-
dc.subject.MESHHepatitis C/immunology-
dc.subject.MESHHepatitis C/pathology-
dc.subject.MESHHepatitis C/virology-
dc.subject.MESHHumans-
dc.subject.MESHInterferon-gamma/analysis-
dc.subject.MESHInterferon-gamma/metabolism-
dc.subject.MESHInterleukin-12/genetics-
dc.subject.MESHInterleukin-12/metabolism-
dc.subject.MESHInterleukin-12/pharmacology-
dc.subject.MESHK562 Cells-
dc.subject.MESHKiller Cells, Natural/drug effects-
dc.subject.MESHKiller Cells, Natural/immunology*-
dc.subject.MESHKiller Cells, Natural/metabolism-
dc.subject.MESHMacrocyclic Compounds/chemistry-
dc.subject.MESHMacrocyclic Compounds/pharmacology-
dc.subject.MESHMicroscopy, Confocal-
dc.subject.MESHNatural Cytotoxicity Triggering Receptor 1/genetics-
dc.subject.MESHNatural Cytotoxicity Triggering Receptor 1/metabolism-
dc.subject.MESHNatural Cytotoxicity Triggering Receptor 3/genetics-
dc.subject.MESHNatural Cytotoxicity Triggering Receptor 3/metabolism-
dc.subject.MESHQuinolines/chemistry-
dc.subject.MESHQuinolines/pharmacology-
dc.subject.MESHRecombinant Proteins/biosynthesis-
dc.subject.MESHRecombinant Proteins/isolation & purification-
dc.subject.MESHRecombinant Proteins/pharmacology-
dc.subject.MESHSerine Proteinase Inhibitors/chemistry-
dc.subject.MESHSerine Proteinase Inhibitors/pharmacology-
dc.subject.MESHThiazoles/chemistry-
dc.subject.MESHThiazoles/pharmacology-
dc.subject.MESHViral Nonstructural Proteins/antagonists & inhibitors-
dc.subject.MESHViral Nonstructural Proteins/genetics-
dc.subject.MESHViral Nonstructural Proteins/metabolism*-
dc.titleHepatitis C virus impairs natural killer cell activity via viral serine protease NS3-
dc.typeArticle-
dc.publisher.locationUnited States-
dc.contributor.collegeCollege of Medicine-
dc.contributor.departmentDept. of Microbiology-
dc.contributor.googleauthorChang Mo Yang-
dc.contributor.googleauthorJoo Chun Yoon-
dc.contributor.googleauthorJeon Han Park-
dc.contributor.googleauthorJae Myun Lee-
dc.identifier.doi10.1371/journal.pone.0175793-
dc.contributor.localIdA03071-
dc.contributor.localIdA01641-
dc.relation.journalcodeJ02540-
dc.identifier.eissn1932-6203-
dc.identifier.pmid28410411-
dc.contributor.alternativeNamePark, Jeon Han-
dc.contributor.alternativeNameLee, Jae Myun-
dc.contributor.affiliatedAuthorLee, Jae Myun-
dc.contributor.affiliatedAuthorPark, Jeon Han-
dc.citation.titlePLoS One-
dc.citation.volume12-
dc.citation.number4-
dc.citation.startPagee0175793-
dc.identifier.bibliographicCitationPLOS ONE, Vol.12(4) : e0175793, 2017-
dc.date.modified2017-11-01-
dc.identifier.rimsid43622-
dc.type.rimsART-
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Microbiology (미생물학교실) > 1. Journal Papers

qrcode

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