Abstract
Most individuals chronically infected with hepatitis C virus (HCV) are asymptomatic during the initial stages of infection and therefore the precise timing of infection is often unknown. Retrospective estimation of infection duration would improve existing surveillance data and help guide treatment. While intra-host viral diversity quantifications such as Shannon entropy have previously been utilized for estimating duration of infection, these studies characterize the viral population from only a relatively short segment of the HCV genome. In this study intra-host diversities were examined across the HCV genome in order to identify the region most reflective of time and the degree to which these estimates are influenced by high-risk activities including those associated with HCV acquisition. Shannon diversities were calculated for all regions of HCV from 78 longitudinally sampled individuals with known seroconversion timeframes. While the region of the HCV genome most accurately reflecting time resided within the NS3 gene, the gene region with the highest capacity to differentiate acute from chronic infections was identified within the NS5b region. Multivariate models predicting duration of infection from viral diversity significantly improved upon incorporation of variables associated with recent public, unsupervised drug use. These results could assist the development of strategic population treatment guidelines for high-risk individuals infected with HCV and offer insights into variables associated with a likelihood of transmission.
Highlights
Most individuals chronically infected with hepatitis C virus (HCV) are asymptomatic during the initial stages of infection and the precise timing of infection is often unknown
Research using whole genome sequencing (WGS) to investigate the relationship between viral diversity and duration of HCV infection among both chronic and acutely infected individuals is needed to compare the longitudinal evolution of each HCV gene region in order to determine which more accurately reflects time
We apply WGS retrospectively to a longitudinally sampled cohort from the Vancouver Injection Drug Users Study (VIDUS) cohort composed of individuals engaging in high-risk behaviours in order to identify regions of the HCV genome that correlate with duration of infection and determine the impacts of recent injection drug use upon these intra-host dynamics
Summary
Most individuals chronically infected with hepatitis C virus (HCV) are asymptomatic during the initial stages of infection and the precise timing of infection is often unknown. Research using WGS to investigate the relationship between viral diversity and duration of HCV infection among both chronic and acutely infected individuals is needed to compare the longitudinal evolution of each HCV gene region in order to determine which more accurately reflects time. How factors such as the transmission mode or how high-risk activities including recent injection drug use impact HCV diversification across the genome have not been adequately addressed. We hypothesized that individuals engaging in high-risk activities such as recent injection drug use would display higher levels of intra-host HCV diversity due to higher propensities for re-infection, mixed infection, and higher variability among founder variants
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