THE ORIGIN OF HEPATITIS-C VIRUS GENOTYPES

For many RNA viruses, relatively recent times of origin of extant viru ses are implied by the high rate of substitution observed in longitudi nal studies, However, extrapolation of short-term rates of substitutio n can give misleading estimates of times of divergence, We show here t hat the common ancestor of different types of hepatitis C virus (HCV) is older than previously thought, The rate of HCV sequence change was measured amongst a cohort of individuals infected following administra tion of anti-D immunoglobulin, Virus sequences were obtained in the E1 and NS5B genes and compared with each other and with sequences from a n infective batch, Taking account of the bias towards synonymous trans ition substitutions, the time of divergence of variants of subtype 1b is estimated to have occurred 70-80 years ago, The numerous subtypes o f HCV are proposed to derive from more than 300 years of endemic infec tion in certain geographical regions, with recent spread of some subty pes to other parts of the world, Estimation of the time of origin of t he major HCV genotypes (types 1-6) is problematic, but our data and an alogy with other viruses suggest that divergence occurred at least 500 -2000 years ago.