Genetically associated CD16(+)56(-) natural killer cell interferon (IFN)-?R expression regulates signaling and is implicated in IFN-?-induced hepatitis C virus decline.

ABSTRACT: Natural killer (NK) cells likely contribute to outcome of acute hepatitis C virus (HCV) infection and interferon (IFN)-induced control of chronic HCV infection. We previously observed IFN-?R and NKp30 expression associated with IFN-?-dependent NK cell activity.Here, we examined CD16(+)56(-), CD16(+)56(+), and CD16(-)56(+) NK cell subset IFN-?R and NKp30 expression in relation to magnitude of HCV genotype 1 decrease during pegylated IFN-? plus ribavirin therapy.We observed greater baseline IFN-?R and NKp30 expression on CD16(+)56(+) and CD16(-)56(+) NK subsets in HCV-infected patients than in healthy control subjects. Baseline CD16(+)56(-) NK IFN-?R expression was associated with IFN-?-induced pSTAT1, and both were associated with magnitude of HCV decrease during pegylated IFN-? plus ribavirin therapy. Baseline CD16(+)56(-) NK IFN-?R expression was associated with race and interleukin 28B genotype, negatively associated with aspartate aminotransferase-to platelet ratio index, and positively associated with increase in NKp30 expression after in vivo IFN-? exposure. Finally, in vitro IFN-?2a-activated NK cytolysis of HCV-infected target cells was in part dependent on NKp30, and CD16(+)56(-) NK cell IFN-?R expression correlated with cytolytic activity.IFN-?R expression on CD16(+)56(-) NK cells during chronic HCV infection may in part be genetically determined, and level of expression regulates IFN-? signaling, which in turn may contribute to control of HCV infection.

SUBMITTER: Conry SJ 

PROVIDER: S-EPMC3295604 | biostudies-literature | 2012 Apr

REPOSITORIES: biostudies-literature