Hepatitis C virus. The importance of viral heterogeneity.

Although recent evidence indicates that the quasispecies nature of HCV constitutes a critical strategy for the virus to survive in the host, the mechanisms of viral persistence remain unknown. Similarly, the correlates of immune protection in a limited proportion of individuals who succeed in clearing HCV are still largely undefined. Understanding the mechanisms of sterilizing immunity is essential for devising preventive measures against HCV and unraveling how the virus eludes such immunity. As in other viral infections, the complex interactions between the virus and the host early in the course of HCV infection probably determine the outcome of the disease (i.e., resolution or persistence). The evidence now accumulated on HCV and other models of viral infection is compatible with the hypothesis that both cellular and humoral components are needed for definitive viral clearance. Nevertheless, detailed studies of the specific cellular and humoral immune responses during the incubation period and the acute phase of hepatitis C, in relation to the viral quasispecies evolution and the clinical outcome, are still lacking both in humans and in the chimpanzee model. Until such studies are performed, most ideas of viral clearance mechanisms remain hypothetical, and the immunologic basis of HCV clearance will continue to be inferred from associations rather than from causal relationships.