Journal
VIRUSES-BASEL
Volume 13, Issue 3, Pages -Publisher
MDPI
DOI: 10.3390/v13030511
Keywords
hepatitis C virus; within-host evolution; mutation frequency; nucleotide diversity
Categories
Funding
- National Science Foundation [1655212]
- National Institute of Health [R01AI134195]
- Division Of Environmental Biology
- Direct For Biological Sciences [1655212] Funding Source: National Science Foundation
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Understanding within-host evolution of Hepatitis C virus (HCV) subtypes is important for predicting viral evolutionary outcomes. This study analyzed within-host mutation frequency patterns of three HCV subtypes, revealing differences in mutation frequencies and nucleotide diversity. Comparison of within-host and between-host selective pressures showed that mutations created within hosts are removed during transmission bottleneck. Natural prevalence of known resistance-associated variants was also found in treatment-naive participants.
Understanding within-host evolution is critical for predicting viral evolutionary outcomes, yet such studies are currently lacking due to difficulty involving human subjects. Hepatitis C virus (HCV) is an RNA virus with high mutation rates. Its complex evolutionary dynamics and extensive genetic diversity are demonstrated in over 67 known subtypes. In this study, we analyzed within-host mutation frequency patterns of three HCV subtypes, using a large number of samples obtained from treatment-naive participants by next-generation sequencing. We report that overall mutation frequency patterns are similar among subtypes, yet subtype 3a consistently had lower mutation frequencies and nucleotide diversity, while subtype 1a had the highest. We found that about 50% of genomic sites are highly conserved across subtypes, which are likely under strong purifying selection. We also compared within-host and between-host selective pressures, which revealed that Hyper Variable Region 1 within hosts was under positive selection, but was under slightly negative selection between hosts, which indicates that many mutations created within hosts are removed during the transmission bottleneck. Examining the natural prevalence of known resistance-associated variants showed their consistent existence in the treatment-naive participants. These results provide insights into the differences and similarities among HCV subtypes that may be used to develop and improve HCV therapies.
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