Hepatitis C Virus Transmission Bottlenecks Analyzed by Deep Sequencing

Wang, G. P., Sherrill-Mix, S. A., Chang, K. M., Quince, C. and Bushman, F. D. (2010) Hepatitis C Virus Transmission Bottlenecks Analyzed by Deep Sequencing. Journal of Virology, 84(12), pp. 6218-6228. (doi: 10.1128/JVI.02271-09)

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: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Quince, Dr Christopher
• Authors: Wang, G. P., Sherrill-Mix, S. A., Chang, K. M., Quince, C., and Bushman, F. D.
• College/School: College of Science and Engineering > School of Engineering > Infrastructure and Environment
• Journal Name: Journal of Virology
• ISSN: 0022-538X