Classification of hepatitis C virus into six major genotypes and a series of subtypes by phylogenetic analysis of the NS-5 region

¹ Department of Medical Microbiology, Medical School, University of Edinburgh, Teviot Place, Edinburgh EH8 9AG, U.K.
² Division of Biology, University of Edinburgh, King's Buildings, West Mains Road, Edinburgh EH9 3JN, U.K.
³ Chiron Corporation, 4560 Horton Street, Emeryville, California 94608, U.S.A.
and⁴ Edinburgh and South East Scotland Blood Transfusion Service, Royal Infirmary of Edinburgh, Lauriston Place, Edinburgh EH3 9HB, U.K.

Hepatitis C virus (HCV) shows substantial nucleotide sequence diversity distributed throughout the viral genome, with many variants showing only 68 to 79% overall sequence similarity to one another. Phylogenetic analysis of nucleotide sequences derived from part of the gene encoding a non-structural protein (NS-5) has provided evidence for six major genotypes of HCV amongst a worldwide collection of 76 samples from HCV-infected blood donors and patients with chronic hepatitis. Many of these HCV types comprised a number of more closely related subtypes, leading to a current total of 11 genetically distinct viral populations. Phylogenetic analysis of other regions of the viral genome produced relationships between published sequences equivalent to those found in NS-5, apart from the more highly conserved 5' non-coding region in which only the six major HCV types, but not subtypes, could be differentiated. A new nomenclature for HCV variants is proposed in this communication that reflects the two-tiered nature of sequence differences between different viral isolates. The scheme classifies all known HCV variants to date, and describes criteria that would enable new variants to be assigned within the classification as they are discovered.

^† Present address: Department of Zoology, University of Oxford, South Parks Road, Oxford OX1 3RE, U.K.