HCV: Written in our DNA.

An inspection of the sequence similarity between the hepatitis C virus (HCV) polyprotein and human proteins revealed a high level of peptide sharing, with a limited number of motifs unique to the virus (i.e., with no counterpart in the human proteome). Using pentapeptide matching, only 214 motifs out of a total of 3,007 (7.11%) identified HCV as nonself compared to the Homo sapiens proteome. However, this virus-versus-human phenetic difference disappeared at the genetic level. Indeed, a BLAST analysis of pentadecameric oligodeoxynucleotide sequences corresponding to the 214 pentapeptides unique to HCV revealed that almost all of them are present in the human genome, located in the non-coding strand, introns, and/or pseudogenes, thus being, as such, untranslatable. The present data warn against using DNA-based vaccines to fight HCV infection and emphasize peptide uniqueness as the molecular basis for designing effective anti-HCV immunotherapeutic approaches.