Exceptional Heterogeneity in Viral Evolutionary Dynamics Characterises Chronic Hepatitis C Virus Infection

PLoS Pathogens

Rebecca Rose¹  Teresa Santantonio²  Philippe Lemey³  Jayna Raghwani⁴  Oliver G. Pybus⁴  Marc A. Suchard⁵  Patrizia Farci⁶  Paul Klenerman⁷  Isabelle Sheridan⁷ 

[1] BioInfoExperts, Thibodaux, Los Angeles, California, United States of America;Clinic of Infectious Diseases, University of Foggia, Foggia, Italy;Department of Microbiology and Immunology, Rega Institute, KU Leuven–University of Leuven, Leuven, Belgium;Department of Zoology, University of Oxford, Oxford, United Kingdom;Departments of Biomathematics, Biostatistics, Human Genetics, University of California, Los Angeles, California, United States of America;Hepatic Pathogenesis Section, Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America;Peter Medawar Building for Pathogen Research, University of Oxford, Oxford, United Kingdom

关键词: HIV-1;    Hepatitis C virus;    Evolutionary rate;    Population genetics;    Phylogenetics;    Viral evolution;    Species diversity;    Viral replication;   

DOI  :  10.1371/journal.ppat.1005894

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

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.

【 授权许可】

CC BY