IMPROVED REACTIVITY OF HEPATITIS-C VIRUS CORE PROTEIN EPITOPES IN A CONFORMATIONAL ANTIGEN-PRESENTING SYSTEM

Recent studies have identified several epitopes in the N-terminal port ion of the nucleocapsid protein which are predominantly recognized by sera of patients infected with hepatitis C virus (HCV). The characteri zation of the sequences recognized by these antibodies and the evaluat ion of their reactivities have been performed mainly with synthetic pe ptides, However, synthetic peptides are notoriously unreliable as anti gens when the immune response is directed against conformational epito pes, In order to improve the detection of antibody responses in HCV-in fected patients, we have evaluated the reactivities of three immunodom inant regions of the HCV core protein (residues 1 to 20, 21 to 40, and 32 to 46) displayed in a conformation-specific manner on the surface of the Flock House virus (FHV) capsid protein. The results obtained wi th these proteins in the analysis of 94 serum samples positive by anti -HCV enzyme-linked immunosorbent assay were then compared with those o btained with the corresponding synthetic peptides, The sequence most r eactive both with the peptide and with the FHV protein was the region from residues 1 to 20, confirming the low conformational requirements for the display of these residues. On the other hand, the already repo rted conformational nature of residues 32 to 46 is in keeping with its observed high reactivity when displayed by the FHV recombinant protei n and with the low reactivity displayed by its corresponding synthetic peptide, Finally, the high reactivity observed for the chimeric prote in displaying the region from residues 21 to 40, as opposed to the res ults obtained with the synthetic peptide, also suggests that this sequ ence contains one or more conformational epitopes whose structures can not be mimicked correctly with synthetic peptides.