Hepatitis C virus shares amino acid sequence similarity with pestiviruses and flaviviruses as well as members of two plant virus supergroups.

Hepatitis C virus (HCV) is an important human pathogen that is associated with transfusion-related non-A, non-B hepatitis. Recently, HCV cDNA was cloned and the nucleotide sequence of approximately three-quarters of the virus genome was determined. A region of the predicted polyprotein sequence was found to share similarity with a nonstructural protein encoded by dengue virus, a member of the flavivirus family. We report here that HCV shares an even greater degree of protein sequence similarity with members of the pestivirus group (i.e., bovine viral diarrhea virus and hog cholera virus), which are thought to be distantly related to the flaviviruses. In addition, we find that HCV shares significant protein sequence similarity with the polyproteins encoded by members of the picornavirus-like and alphavirus-like plant virus supergroups. These data suggest that HCV may be evolutionarily related to both plant and animal viruses.