Cross-reactivity and clinical impact of the antibody response to hepatitisC virus second envelope glycoprotein (E2)

The genotype of hepatitis C virus (HCV) can profoundly affect the success o f antiviral therapy for HCV infection. A possible contributing factor is a varied immune response elicited by infection with different HCV genotypes. In this study, full-length E2 proteins of HCV genotypes la, 1b, 2a, and 2b were used to determine the fraction of the humoral immune response to HCV E 2 that is genotype specific. Greater than 90% of all infected individuals h ad serum antibodies to the four E2 proteins. Overall, individuals infected with genotype la or 1 b were characterized by variable immune responses to HCV E2 with relatively high amounts of cross-reactivity with other E2 prote ins. Individuals infected with genotype 2a or 2b exhibited a strong prefere ntial reactivity to genotype 2a and 2b E2 proteins. Individuals with elevat ed titers to HCV E2 were more likely to be infected with genotype 2a and ha d a significantly lower median viral load. These findings indicate that the antibody response to HCV E2 is affected by the genotype of the virus and t hat induction of a strong humoral immune response to HCV E2 may contribute to a decreased viral load. (C) 2001 Wiley-Liss, Inc.