Intra-host genetic heterogeneity of hepatitis C virus and biomedical implications

The HCV genome exhibits significant intra-host genetic heterogeneity as the result of accumulation of mutations during viral replication. At each point in time during the infection, the viral population is composed of a dominant master sequence and a number of sequences diverging from the master sequence to various extents (the viral quasi-species). The quasispecies is a complex, dynamic distribution of nonidentical, but related, replicons. In these populations, viral variants may undergo very large changes in their fitness (the replicative adaptability of an organism to its environment), including dramatic fitness loss and important fitness gains. The biological impact of this event may theoretically include modifications of tropism, appearance of escape mutants, changes in pathogenic potential, and resistance to antiviral agents. A growing body of molecular and clinical data currently suggests that both inter- and intra-host genetic heterogeneity of HCV have crucial biological and medical implications, influencing not only infection prevention, but also clinical progression of chronic liver disease in persistently infected subjects, HCV infection of non-liver cells, and response to the anti-viral therapy.