Single-virion sequencing of lamivudine-treated HBV populations reveal population evolution dynamics and demographic history

BMC Genomics

Research Article

Niranjan Nagarajan¹  Yuan O. Zhu¹  Chen Hao Li¹  Shuzhen Hong¹  Andreas Wilm¹  Paola Florez de Sessions¹  Pauline P. K. Aw¹  Martin Hibberd²  Lewis Z. Hong³  Lee Xian See³  William F. Burkholder³  Stephane Hue⁴  Seng Gee Lim⁵ 

[1] Genome Institute of Singapore, 138672, Singapore, Singapore;Genome Institute of Singapore, 138672, Singapore, Singapore;London School of Hygiene and Tropical Medicine, London, UK;Institute of Molecular and Cell Biology, 138673, Singapore, Singapore;London School of Hygiene and Tropical Medicine, London, UK;National University Hospital, 119074, Singapore, Singapore;

关键词: Single-virion sequencing;    Viral evolution;    Adaptation regime;    Drug resistance;    Chronic hepatitis B;    Population demographic history;    Bayesian MCMC;   

DOI  :  10.1186/s12864-017-4217-1

 received in 2017-05-08, accepted in 2017-10-16,  发布年份 2017

来源: Springer

【 摘 要 】

BackgroundViral populations are complex, dynamic, and fast evolving. The evolution of groups of closely related viruses in a competitive environment is termed quasispecies. To fully understand the role that quasispecies play in viral evolution, characterizing the trajectories of viral genotypes in an evolving population is the key. In particular, long-range haplotype information for thousands of individual viruses is critical; yet generating this information is non-trivial. Popular deep sequencing methods generate relatively short reads that do not preserve linkage information, while third generation sequencing methods have higher error rates that make detection of low frequency mutations a bioinformatics challenge. Here we applied BAsE-Seq, an Illumina-based single-virion sequencing technology, to eight samples from four chronic hepatitis B (CHB) patients – once before antiviral treatment and once after viral rebound due to resistance.ResultsWith single-virion sequencing, we obtained 248–8796 single-virion sequences per sample, which allowed us to find evidence for both hard and soft selective sweeps. We were able to reconstruct population demographic history that was independently verified by clinically collected data. We further verified four of the samples independently through PacBio SMRT and Illumina Pooled deep sequencing.ConclusionsOverall, we showed that single-virion sequencing yields insight into viral evolution and population dynamics in an efficient and high throughput manner. We believe that single-virion sequencing is widely applicable to the study of viral evolution in the context of drug resistance and host adaptation, allows differentiation between soft or hard selective sweeps, and may be useful in the reconstruction of intra-host viral population demographic history.

【 授权许可】

CC BY   
© The Author(s). 2017