Locations of antibody binding sites within conserved regions of the hepatitis C virus core protein

The binding sites for human antibodies recognising antigenic domains within the hepatitis C virus (HCV) core protein were analyzed using synthetic peptides. Omission peptide analogues where a pair of residues was sequentially omitted were produced corresponding to the regions 1-18, 11-28, 21-38, 51-68, and 101-118. The N-terminal part of HCV core was found to contain three distinct antibody binding sites, which includes the previously reported one at residues 9-16. The other two were located at residues 19-26 and residues 29-34. Within the region 51-68 two overlapping sites were found, the first at residues 51-60 and the second at residues 59-68. Within the region 101-118, residues 107-114 were identified as the binding site, which contains two residues differing between genotypes I/II and III/VI. Thus the HCV core protein contains at least six distinct linear antibody binding sites, located at regions highly conserved between the genotypes of HCV. The human recognition of these regions show a variation with respect to the amino- and carboxy-terminal extension of each individual binding site. These findings will have implications for the prediction of the structure of the HCV core protein, since these antibody binding sequences are likely to be more or less accessible from the exterior of either, or both, of the native HCV core and its precursor polyprotein.