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 imp ortance this information would provide in predicting clinical outcomes and controlling spread of HCV in the future. However, in the absence of histori cal and archaeological records of infection, the evolution of HCV and other human hepatitis viruses can only be inferred indirectly from their epidemi ology and by genetic analysis of contemporary virus populations. Some infor mation on the history of the latter may be obtained by dating the time of d ivergence of various genotypes of HCV, hepatitis B virus (HBV) and the nonp athogenic hepatitis G virus (HGV)/GB virus-C (GBV-C). However, the relative ly recent times predicted for the origin of these viruses fit poorly with t heir epidemiological distributions and the recent evidence for species-asso ciated 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 lat ter observations may be the result of constraints on sequence change peculi ar to viruses with single-stranded genomes, or with overlapping reading fra mes. Large population sizes and intense selection pressures that optimize f itness may be the factors that set virus evolution apart from that of their hosts.