Source

Department of Zoology, University of Oxford, Oxford, UK, OX13PS.

Abstract

Chronic hepatitis C virus (HCV) infection can lead to liver cirrhosis in up to 20% of individuals, often requiring liver transplantation. Although the new liver is known to be rapidly re-infected, the dynamics and source of the re-infecting virus(es) are unclear, resulting in some confusion concerning the relationship between clinical outcome and viral characteristics. To clarify the dynamics of liver re-infection, longitudinal serum viral samples from 10 transplant patients were studied. Part of the E1/E2 region was sequenced and advanced phylogenetic analysis methods were used in a multi-parameter analysis to determine the history and ancestry of re-infecting lineages. Our results demonstrated the complexity of HCV evolutionary dynamics following liver transplant, in which a large diverse population of viruses is transmitted and maintained for months to years. As many as 30 independent lineages in a single patient were found to re-infect the new liver. Several later post-transplant lineages were more closely related to older pre-transplant viruses than to viruses detected immediately post-transplant. Although our data are consistent with a number of interpretations, persistence of high viral genetic variation over long periods of time requires an active mechanism. We discuss possible scenarios, including frequency-dependent selection or variation in selective pressure among viral sub-populations, i.e. population structure. The latter hypothesis, if correct, could have relevance to the success of newer direct-acting antiviral therapies.