View : 465 Download: 129

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

Title
Hepatitis C virus impairs natural killer cell activity via viral serine protease NS3
Authors
Yang C.M.Yoon J.C.Park J.H.Lee J.M.
Ewha Authors
윤주천
SCOPUS Author ID
윤주천scopus
Issue Date
2017
Journal Title
PLoS ONE
ISSN
1932-6203JCR Link
Citation
PLoS ONE vol. 12, no. 4
Publisher
Public Library of Science
Indexed
SCIE; SCOPUS WOS scopus
Document Type
Article
Abstract
Hepatitis 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. © 2017 Yang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
DOI
10.1371/journal.pone.0175793
Appears in Collections:
의과대학 > 의학과 > Journal papers
Files in This Item:
Hepatitis C virus impairs.pdf(1.99 MB) Download
Export
RIS (EndNote)
XLS (Excel)
XML


qrcode

BROWSE