Phylogeny and molecular evolution of the hepatitis C virus

•The state-of-the art in HCV phylogeny and molecular evolution.•Molecular evolution of HCV in the context of host–virus interplay.•Mechanisms of HCV evolution.•Implications of HCV phylogeny and evolution for the virus classification and disease epidemiology and control. The hepatitis C virus (HCV) is a globally prevalent human pathogen that causes persistent liver infections in most infected individuals. HCV is classified into seven phylogenetically distinct genotypes, which have different geographical distributions and levels of genetic diversity. Some of these genotypes are endemic and highly divergent, whereas others disseminate rapidly on an epidemic scale but display lower variability. HCV phylogeny has an important impact on disease epidemiology and clinical practice because the viral genotype may determine the pathogenesis and severity of the resultant chronic liver disease. In addition, there is a clear association between the HCV genotype and its susceptibility to antiviral treatment. Similarly to other RNA viruses, in a single host, HCV exists as a combination of related but genetically different variants. The whole formation is the actual target of selection exerted by a host organism and antiviral therapeutics. The genetic structure of the viral population is largely shaped by mutations that are constantly introduced during an error-prone replication. However, it appears that genetic recombination may also contribute to this process. This heterogeneous collection of variants has a significant ability to evolve towards the fitness optimum. Interestingly, negative selection, which restricts diversity, emerges as an essential force that drives HCV evolution. It is becoming clear that HCV evolves to become stably adapted to the host environment. In this article we review the HCV phylogeny and molecular evolution in the context of host–virus interactions.