Comparative analysis of the molecular mechanisms of recombination in hepatitis C virus

• HCV can recombine at least 0.4–4×10–5 times per genome per replication cycle.
• Non-replicative HCV recombination can efficiently produce non-homologous recombinants.
• Replicative HCV recombination generates mostly homologous recombinants.
• Similarities among RNA viruses suggest common recombination molecular mechanisms.

Genetic recombination is an important evolutionary mechanism for RNA viruses. The significance of this phenomenon for hepatitis C virus (HCV) has recently become evident, with the identification of circulating recombinant forms in HCV-infected individuals and by novel data from studies permitted by advances in HCV cell culture systems and genotyping protocols. HCV is readily able to produce viable recombinants, using replicative and non-replicative molecular mechanisms. However, our knowledge of the required molecular mechanisms remains limited. Understanding how HCV recombines might be instrumental for a better monitoring of global epidemiology, to clarify the virus evolution, and evaluate the impact of recombinant forms on the efficacy of oncoming combination drug therapies. For the latter, frequency and location of recombination events could affect the efficacy of multidrug regimens. This review will focus on current data available on HCV recombination, also in relation to more detailed data from other RNA viruses.