Comparative Analysis of Within-Host Mutation Patterns and Diversity of Hepatitis C Virus Subtypes 1a, 1b, and 3a

被引:1
|
作者
Tisthammer, Kaho H. [1 ]
Dong, Weiyan [2 ]
Joy, Jeffrey B. [2 ,3 ,4 ]
Pennings, Pleuni S. [1 ]
机构
[1] San Francisco State Univ, Dept Biol, San Francisco, CA 94132 USA
[2] BC Ctr Excellence HIV AIDS, Vancouver, BC V6Z 1Y6, Canada
[3] Univ British Columbia, Div Infect Dis, Dept Med, Vancouver, BC V5Z 3J5, Canada
[4] Univ British Columbia, Bioinformat Programme, Vancouver, BC V6T 1Z4, Canada
来源
VIRUSES-BASEL | 2021年 / 13卷 / 03期
基金
美国国家科学基金会;
关键词
hepatitis C virus; within-host evolution; mutation frequency; nucleotide diversity; GLOBAL EPIDEMIOLOGY; HCV GENOTYPE; VIRAL LOAD; RESISTANCE; UPDATE; ASSOCIATION; INFECTION; CPG;
D O I
10.3390/v13030511
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
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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页数:15
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