TY - JOUR
T1 - Hepatitis C virus (HCV) eradication with interferon-free direct-acting antiviral-based therapy results in KLRG1+ HCV-specific memory natural killer cells
AU - Wijaya, Ratna S.
AU - Read, Scott A.
AU - Selvamani, Sakthi P.
AU - Schibeci, Stephen
AU - Azardaryany, Mahmoud K.
AU - Ong, Adrian
AU - Poorten, David van der
AU - Lin, Rita
AU - Douglas, Mark W.
AU - George, Jacob
AU - Ahlenstiel, Golo
N1 - Publisher Copyright:
© 2020 The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: [email protected].
PY - 2021/4/1
Y1 - 2021/4/1
N2 - Direct acting antiviral therapies rapidly clear chronic hepatitis C virus (HCV) infection and restore natural killer (NK) cell function. We investigated NK cell memory formation following HCV clearance by examining NK cell phenotype and responses from control and chronic HCV patients before and after therapy following sustained virologic response at 12 weeks post-therapy (SVR12). NK cell phenotype at SVR12 differed significantly from paired pre-treatment samples, with an increase in maturation markers CD16, CD57 and KLRG1. HCV patients possessed stronger cytotoxic responses against HCV infected cells as compared to healthy controls; a response that further increased following SVR12. The antigen-specific response was mediated by KLRG1+ NK cells, as demonstrated by increased degranulation and proliferation in response to HCV antigen only. Our data suggest that KLRG1+ HCVspecific memory NK cells develop following viral infection, providing insight into their role in HCV clearance and relevance with regard to vaccine design.
AB - Direct acting antiviral therapies rapidly clear chronic hepatitis C virus (HCV) infection and restore natural killer (NK) cell function. We investigated NK cell memory formation following HCV clearance by examining NK cell phenotype and responses from control and chronic HCV patients before and after therapy following sustained virologic response at 12 weeks post-therapy (SVR12). NK cell phenotype at SVR12 differed significantly from paired pre-treatment samples, with an increase in maturation markers CD16, CD57 and KLRG1. HCV patients possessed stronger cytotoxic responses against HCV infected cells as compared to healthy controls; a response that further increased following SVR12. The antigen-specific response was mediated by KLRG1+ NK cells, as demonstrated by increased degranulation and proliferation in response to HCV antigen only. Our data suggest that KLRG1+ HCVspecific memory NK cells develop following viral infection, providing insight into their role in HCV clearance and relevance with regard to vaccine design.
KW - hepatitis C virus
KW - killer cells
KW - natural immunity
UR - http://hdl.handle.net/1959.7/uws:57052
U2 - 10.1093/infdis/jiaa492
DO - 10.1093/infdis/jiaa492
M3 - Article
C2 - 32777077
SN - 0022-1899
VL - 223
SP - 1183
EP - 1195
JO - Journal of Infectious Diseases
JF - Journal of Infectious Diseases
IS - 7
ER -
