Distinct Subtypes of Hepatitis C Virus Defined by Antibodies Directed to the Putative Core, NS4, and NS5 Region Polypeptides

At least six distinct genotypes of the hepatitis C virus (HCV) have been identified by nucleotide sequence comparison of isolates from different areas of the world [1,2]. Phylogenetic analysis of all previously published HCV sequences revealed three to four distinct types of sequences [3]. Phylogenetic analysis of each of the coding regions confirmed HCV variants in regions such as the Far East and USA/Europe. We examined the possibility that HCV may have serologically definable subtypes. The major epitopes of the polyprotein of HCV-1 (la strain) were determined with 3000 octapeptides on a pin solid-phase pepscan study [4]. The major epitope regions from HCV-1 core, NS4, and NS5 regions were chosen for sequence comparison between different genotype sequences. Three antigenic areas from the core, NS4, and NS5 regions of HCV-1, which contain nonconserved sequences compared to other HCV types, were selected for peptide synthesis. Three enzyme-linked immunosorbent assays (ELISAs) were prepared using recombinant antigens and synthetic peptides deduced from the structure region of the core and non-structural regions of the NS4 and NS5 antigens. The antibody response to type-specific epitopes and conserved epitopes was examined in all three regions. The results indicate that there are serotype-specific epitopes in the core, NS4, and NS5 regions. These serotype epitopes can be linked to type-specific genotype HCV variants by a type-specific polymerase chain reaction (PCR) primer study. The epidemiology of some type-specific serotype variants was also studied.