Hepatitis C virus (HCV) remains a global public health problem even though more than 95% of infections can be cured by treatment with direct-acting antiviral agents. Resolution of viremia post antiviral therapy does not lead to protective immunity and therefore reinfections can occur. Immune cell detection of HCV activates signaling pathways that produce interferons and trigger the innate immune response against the virus, preventing HCV replication and spread. Cells in the innate immune system, including natural killer, dendritic, and Kupffer cells, interact with infected hepatocytes and present viral antigens to T and B cells where their effector responses contribute to infection outcome. Despite the immune activation, HCV can evade the host response and establish persistent infection. Plans to understand the correlates of protection and strategies to activate proper innate and adaptive immune responses are needed for development of an effective prophylactic vaccine that stimulates protective immunity and limits HCV transmission.
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