HCV and innate immunity

Hepatitis C virus (HCV) is a single-strand, positive sense RNA virus belonging to the flaviviridae family. HCV develops persistent infection in >70% of infected patients, and eventually causes chronic hepatitis, cirrhosis, and hepatocellular carcinoma in some patients. Once chronic infection is established in patients with HCV, spontaneous viral clearance fails, although how HCV remains persistently infecting the liver is largely unknown. Insufficient immune response, involving antiviral innate immune response including dendritic cells (DCs), has been focused. A number of controversial studies have been reported as to HCV genome replication and HCV-mediated immune responses in human DCs. A tantalizing point of these earlier studies is the lack of the system for viral propagation in HCV. Recently, an in vitro system was exploited to propagate HCV particles using the JFH1 strain. In this review, we review the previous reports about the subversion of innate immunity by HCV and show the innate response of monocyte-derived dendritic cells (MoDCs) against the JFH1 strain. We could not observe HCV direct interaction with MoDC maturation. MoDCs maturated by phagocytosing HCV-infected apoptotic cells containing virus-derived dsRNA, which interacted with TLR3 in the phagosomes. All of these data suggests the importance of TLR3 signal for the induction of anti-HCV innate immunity.