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2016 ; 12
(9
): e1005894
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Exceptional Heterogeneity in Viral Evolutionary Dynamics Characterises Chronic
Hepatitis C Virus Infection
#MMPMID27631086
Raghwani J
; Rose R
; Sheridan I
; Lemey P
; Suchard MA
; Santantonio T
; Farci P
; Klenerman P
; Pybus OG
PLoS Pathog
2016[Sep]; 12
(9
): e1005894
PMID27631086
show ga
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.