Hepatitis C virus (HCV) remains a public health problem of global importance, even in the
era of potent directly-acting antiviral drugs. In this chapter, I discuss immune responses to acute and
chronic HCV infection. The outcome of HCV infection is influenced by viral strategies that limit or
delay the initiation of innate antiviral responses. This delay may enable HCV to establish widespread
infection long before the host mounts effective T and B cell responses. HCV’s genetic agility, resulting
from its high rate of replication and its error prone replication mechanism, enables it to evade immune
recognition. Adaptive immune responses fail to keep up with changing viral epitopes. Neutralizing
antibody epitopes may be hidden by decoy structures, glycans, and lipoproteins. T cell responses
fail due to changing epitope sequences and due to exhaustion, a phenomenon that may have evolved
to limit immune-mediated pathology. Despite these difficulties, innate and adaptive immune mechanisms
do impact HCV replication. Immune-mediated clearance of infection is possible, occurring in
20-50% of people who contract the disease. New developments raise hopes for effective immunological
interventions to prevent or treat HCV infection.
Keywords: Hepatitis C virus, immune response, innate immunity, T cell exhaustion, interferon lambda, neutralizing antibodies.
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