Subtyping of hepatitis C virus with high resolution mass spectrometry

A proteotyping approach using high resolution mass spectrometry has been applied, for the first time, to subtype the hepatitis C virus based upon detection of one or more signature peptides derived from the E1 and E2 envelope glycoproteins. These signature peptides represent conserved peptide segments within these proteins for particular subtypes of the virus that are found to be unique in mass when compared with the theoretical masses for all peptide segments of translated HCV proteins within a specifically constructed database. The successful application of the approach to three different subtypes of the virus (i.e., 1a, 1b and 2b) is demonstrated for protein and whole virus proteolytic digests. The approach has the potential to replace existing PCR-based subtyping by offering a more direct and cost comparable strategy that is not challenged by mixed infection scenarios.