Hepatitis C virus transmission bottlenecks analyzed by deep sequencing

Wang, Gary P., Sherrill-Mix, Scott A., Chang, Kyong Mi, Quince, Chris and Bushman, Frederic D. (2010) Hepatitis C virus transmission bottlenecks analyzed by deep sequencing. Journal of Virology, 84 (12). pp. 6218-6228. ISSN 0022-538X

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Abstract

Hepatitis C virus (HCV) replication in infected patients produces large and diverse viral populations, which give rise to drug-resistant and immune escape variants. Here, we analyzed HCV populations during transmission and diversification in longitudinal and cross-sectional samples using 454/Roche pyrosequencing, in total analyzing 174,185 sequence reads. To sample diversity, four locations in the HCV genome were analyzed, ranging from high diversity (the envelope hypervariable region 1 [HVR1]) to almost no diversity (the 5′ untranslated region [UTR]). For three longitudinal samples for which early time points were available, we found that only 1 to 4 viral variants were present, suggesting that productive infection was initiated by a very small number of HCV particles. Sequence diversity accumulated subsequently, with the 5′ UTR showing almost no diversification while the envelope HVR1 showed >100 variants in some subjects. Calculation of the transmission probability for only a single variant, taking into account the measured population structure within patients, confirmed initial infection by one or a few viral particles. These findings provide the most detailed sequence-based analysis of HCV transmission bottlenecks to date. The analytical methods described here are broadly applicable to studies of viral diversity using deep sequencing.

Item Type: Article
Uncontrolled Keywords: microbiology,immunology,insect science,virology,sdg 3 - good health and well-being ,/dk/atira/pure/subjectarea/asjc/2400/2404
Faculty \ School: Faculty of Science > School of Biological Sciences
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Depositing User: LivePure Connector
Date Deposited: 12 Sep 2022 11:30
Last Modified: 23 Sep 2022 02:53
URI: https://ueaeprints.uea.ac.uk/id/eprint/88127
DOI: 10.1128/JVI.02271-09

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