Diversification of hypervariable region 1 of hepatitis C virus after liver transplantation

Liver transplantation represents a unique model for studying hepatitis C virus (HCV) evolution. In the current study, we estimated the dynamics of HCV quasispecies evolution over a period of 2.5 years both in sera and in tissues, including three different anatomic sites of the liver in a patient undergoing liver transplantation. The patient displayed an extremely homologous virus population in either serum or liver at each time point after liver transplantation. However, there was a successive diversification of hypervariable region 1 (HVR1) of HCV under such an im-munocompromised status and the preexistence of matching HVR1 antibodies. This distinct evolutionary pattern of HVR1 suggests that immunosuppressed status does contribute to diminished genetic diversity of HVR1 at a given time point after liver transplantation. However, the dramatic diversification of HVR1 sequence over time is mainly due to the adaptation of new replicative site, the donor liver, indicating that HCV may obtain the higher replication fitness by mutating HVR1 domain.