Innate Immunity in Hepatitis C Virus Infection

Activation and viral control of the innate immune response are hallmarks of hepatitis C virus (HCV) infection and are major determinants of spontaneous clearance or progression to chronic infection and liver disease. In this review, we provide a contemporary overview of how HCV is sensed by the host cell to trigger innate immune activation and the mechanisms deployed by the virus to evade this response. Type I and III interferons (IFNs) are crucial mediators of antiviral innate immunity against HCV, and we specifically highlight the importance of IFN-λ host genetics for the outcome of HCV infection. Last, we focus on the proinflammatory responses elicited by HCV infection and describe our current understanding of how interleukin (IL)-1β signaling and cross talk between the IL-1β and IFN signaling pathways lead to sustained inflammation and increased risk of liver pathology.