ANTIGENIC VARIATION OF CORE, NS3, AND NS5 PROTEINS AMONG GENOTYPES OFHEPATITIS-C VIRUS

Assays that detect antibody to hepatitis C virus (HCV) are used to scr een blood donors and patients with hepatitis. Current enzyme-linked im munosorbent assay (ELISA)-based methods are invariably based upon anti gens from expressed recombinant proteins or oligopeptides from HCV typ e 1. Some HCV antigens used in screening assays are coded by regions o f the HCV genome that show extensive variability; therefore, HCV type 1-based assays may be less effective for the detection of antibody eli cited by infection with other genotypes. In this study, we have measur ed antibody reactivity of sera from 110 hepatitis C patients infected with type Ib, 3a, or 4a to genotype-specific and cross-reactive epitop es present in recombinant proteins from HCV genotypes Ib (core, NS3, a nd NS5), 3a (NS3, NS5), and 4a (core, NS3), corresponding to those use d in current third-generation screening ELISAs. By comparing the serol ogical reactivities of sera to type-homologous and type-heterologous a ntigens, we detected a significant type-specific component to the reac tivity to NS3 (61 to 77% of the total reactivity) and NS5 (60% of the total reactivity). Furthermore, despite the similarities In the amino acid sequences of the core antigens of type Ib and type 4a, we also fo und significantly greater reactivity to type-homologous antigens, with approximately 25% of reactivity being type specific. These findings a re consistent with previous findings of fivefold weaker reactivity of sera from HCV type 2- and HCV type 3-infected blood donors in the curr ently used third-generation ELISAs and suggest that these assays are s uboptimal for screening populations in which the predominant genotype is not type 1.