Immune Control of HCV Infection
In this chapter, I summarize current knowledge regarding the mechanisms by which infected cells and the immune system control HCV replication and spread, and how HCV infection persists despite targeting by innate antiviral mechanisms and the adaptive immune system. Recognition of viral RNA stimulates infected cells to produce interferons, which are potent antiviral mediators, but HCV proteins may disable RNA recognition and interferon response mechanisms. Spontaneous HCV clearance is associated with a broadly focused and robust HCV-specific T cell response. However, T cell mediated control of HCV is frequently hampered by viral sequence evolution, exhaustion of HCV-specific T cells, and tolerance mechanisms that protect the liver from immunologically mediated pathology. HCV-specific antibodies can limit but not completely ablate HCV infection of new target cells. As for T cell responses, the efficacy of antibody responses may be limited by viral evolution. Interferons and some soon-to-be available antiviral drugs may enhance innate and adaptive immune mechanisms.