Hepatitis C virus and innate immunity: Taking a fresh look into an old issue

The innate immune response represents the first line of defense against hepatitis C virus (HCV) infection. The response is an early, coordinated effort orchestrated by host interferon (IFN) production, natural killer cell activation, and dendritic cell maturation, which, when effective, primes a successful adaptive immune response, leading to resolution of infection. Numerous mechanisms allow subversion of innate immunity, often establishing chronicity and resistance to conventional antiviral therapy. Recent groundbreaking studies examining viral evasion of host defenses and genetic host determinants of response to IFN have advanced our understanding of the innate immune response to HCV. This has provided the framework for individualized treatment approaches and the development of novel therapeutics aimed at restoring innate immune signaling during chronic infection. The objective of this report is to review advances in our understanding of HCVand host innate immune defenses, and to highlight their clinical translation.