The Effects of Hepatitis C Virus Core Protein on Functional Responses in the NK Cell Line YTS

Hepatitis C virus infection affects more than 170 million people worldwide. More than 80% of the patients are not able to eliminate the virus and progress to a chronic infection that usually culminates in complications such as cirrhosis and/or hepatocellular carcinoma. Although the adaptive immune response has been widely shown to be essential for viral clearance, the role of natural killer (NK) cells is not clearly understood. In this study, the effect of HCV core protein is examined on NK cell function, i.e., cytotoxicity and cytokine secretion. The expression of core protein in the YTS NK cell line led to an increase in the percentage of apoptotic cells soon after transduction. The surviving cells exhibited decreased cytotoxicity associated with decreases in perforin and granzyme B expression. Furthermore, the HCV core protein–transduced YTS NK cells had reduced IFNγ production as well as an altered surface receptor expression pattern. These features may correspond to a state of functional anergy similar to that seen in T cells transduced with HCV core protein. Together, these data suggest that HCV core protein may alter NK cell function.