Cookies on this website

We use cookies to ensure that we give you the best experience on our website. If you click 'Accept all cookies' we'll assume that you are happy to receive all cookies and you won't see this message again. If you click 'Reject all non-essential cookies' only necessary cookies providing core functionality such as security, network management, and accessibility will be enabled. Click 'Find out more' for information on how to change your cookie settings.

The treatment of HCV infection has seen significant progress, particularly since the approval of new direct-acting antiviral drugs. However these clinical achievements have been made despite an incomplete understanding of HCV replication and within-host evolution, especially compared with HIV-1. Here, we undertake a comprehensive analysis of HCV within-host evolution during chronic infection by investigating over 4000 viral sequences sampled longitudinally from 15 HCV-infected patients. We compare our HCV results to those from a well-studied HIV-1 cohort, revealing key differences in the evolutionary behaviour of these two chronic-infecting pathogens. Notably, we find an exceptional level of heterogeneity in the molecular evolution of HCV, both within and among infected individuals. Furthermore, these patterns are associated with the long-term maintenance of viral lineages within patients, which fluctuate in relative frequency in peripheral blood. Together, our findings demonstrate that HCV replication behavior is complex and likely comprises multiple viral subpopulations with distinct evolutionary dynamics. The presence of a structured viral population can explain apparent paradoxes in chronic HCV infection, such as rapid fluctuations in viral diversity and the reappearance of viral strains years after their initial detection.

Original publication

DOI

10.1371/journal.ppat.1005894

Type

Journal article

Journal

PLoS Pathog

Publication Date

09/2016

Volume

12

Keywords

Evolution, Molecular, Female, Follow-Up Studies, HIV Infections, HIV-1, Hepacivirus, Hepatitis C, Chronic, Humans, Male, Virus Replication