The origin and evolution of hepatitis viruses in humans

The spread and origins of hepatitis C virus (HCV) in human populations have been the subject of extensive investigations, not least because of the importance this information would provide in predicting clinical outcomes and controlling spread of HCV in the future. However, in the absence of historical and archaeological records of infection, the evolution of HCV and other human hepatitis viruses can only be inferred indirectly from their epidemiology and by genetic analysis of contemporary virus populations. Some information on the history of the latter may be obtained by dating the time of divergence of various genotypes of HCV, hepatitis B virus (HBV) and the nonpathogenic hepatitis G virus (HGV)/GB virus-C (GBV-C). However, the relatively recent times predicted for the origin of these viruses fit poorly with their epidemiological distributions and the recent evidence for species-associated variants of HBV and HGV/GBV-C in a wide range of nonhuman primates. The apparent conservatism of viruses over long periods implied by these latter observations may be the result of constraints on sequence change peculiar to viruses with single-stranded genomes, or with overlapping reading frames. Large population sizes and intense selection pressures that optimize fitness may be the factors that set virus evolution apart from that of their hosts.