Hepatitis C virus and antiviral innate immunity: who wins at tug-of-war?

Hepatitis C virus (HCV) is a major human pathogen of chronic hepatitis and related liver diseases. Innate immunity is the first line of defense against invading foreign pathogens, and its activation is dependent on the recognition of these pathogens by several key sensors. The interferon (IFN) system plays an essential role in the restriction of HCV infection via the induction of hundreds of IFN-stimulated genes (ISGs) that inhibit viral replication and spread. However, numerous factors that trigger immune dysregulation, including viral factors and host genetic factors, can help HCV to escape host immune response, facilitating viral persistence. In this review, we aim to summarize recent advances in understanding the innate immune response to HCV infection and the mechanisms of ISGs to suppress viral survival, as well as the immune evasion strategies for chronic HCV infection.