Phylogenomic analysis unravels evolution of yellow fever virus within hosts

Chen Chen; Dong Jiang; Ming Ni; Jing Li; Zhihai Chen; Jingyuan Liu; Hanhui Ye; Gary Wong; Wei Li; Yuanyuan Zhang; Beibei Wang; Yuhai Bi; Danying Chen; Ping Zhang; Xuesen Zhao; Yaxian Kong; Weifeng Shi; Pengcheng Du; Gengfu Xiao; Juncai Ma; George F Gao; Jie Cui; Fujie Zhang; Wenjun Liu; Xiaochen Bo; Ang Li; Hui Zeng; Di Liu

doi:10.1371/journal.pntd.0006738

Phylogenomic analysis unravels evolution of yellow fever virus within hosts

PLoS Negl Trop Dis. 2018 Sep 6;12(9):e0006738. doi: 10.1371/journal.pntd.0006738. eCollection 2018 Sep.

Authors

Chen Chen^{1

2}, Dong Jiang^{1

2}, Ming Ni³, Jing Li⁴, Zhihai Chen^{1

2

5}, Jingyuan Liu⁶, Hanhui Ye⁷, Gary Wong⁴, Wei Li⁴, Yuanyuan Zhang^{1

2}, Beibei Wang^{1

2}, Yuhai Bi⁴, Danying Chen^{1

2}, Ping Zhang⁷, Xuesen Zhao^{1

2}, Yaxian Kong^{1

2}, Weifeng Shi⁸, Pengcheng Du^{1

2}, Gengfu Xiao⁹, Juncai Ma⁴, George F Gao^{4

10

11}, Jie Cui⁹, Fujie Zhang^{1

2

5}, Wenjun Liu^{4

10}, Xiaochen Bo³, Ang Li^{1

2}, Hui Zeng^{1

2}, Di Liu^{4

9

10}

Affiliations

¹ Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, China.
² Beijing Key Laboratory of Emerging Infectious Diseases, Beijing, China.
³ Beijing Institute of Radiation Medicine, Beijing, China.
⁴ Institute of Microbiology, Chinese Academy of Sciences, Beijing, China.
⁵ Clinical Center for Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, China.
⁶ Department of Intensive Care Unit, Beijing Ditan Hospital, Capital Medical University, Beijing, China.
⁷ Fuzhou Infectious Disease Hospital of Fujian Medical University, Fuzhou, China.
⁸ Institute of Pathogen Biology, Taishan Medical College, Taian, China.
⁹ Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China.
¹⁰ Medical School, University of Chinese Academy of Sciences, Beijing, China.
¹¹ Chinese Center for Disease Control and Prevention (China CDC), Beijing, China.

Abstract

The yellow fever virus (YFV) recently reemerged in the large outbreaks in Africa and Brazil, and the first imported patients into Asia have recalled the concerns of YFV evolution. Here we show phylogenomics of YFV with serial clinical samples of the 2016 YFV infections. Phylogenetics exhibited that the 2016 strains were close to Angola 1971 strains and only three amino acid changes presented new to other lineages. Deep sequencing of viral genomes discovered 101 intrahost single nucleotide variations (iSNVs) and 234 single nucleotide polymorphisms (SNPs). Analysis of iSNV distribution and mutated allele frequency revealed that the coding regions were under purifying selection. Comparison of the evolutionary rates estimated by iSNV and SNP showed that the intrahost rate was ~2.25 times higher than the epidemic rate, and both rates were higher than the long-term YFV substitution rate, as expected. In addition, the result also hinted that short viremia duration of YFV might further hinder the evolution of YFV.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Evolution, Molecular*
Genome, Viral
High-Throughput Nucleotide Sequencing
Humans
Mutation Rate
Phylogeny*
Polymorphism, Single Nucleotide*
Yellow Fever / virology
Yellow fever virus / classification*
Yellow fever virus / genetics*
Yellow fever virus / isolation & purification

Grants and funding

This work was supported by Grants from China Ministry of Science and Technology Key Research and Development Program [2016YFC1200804 and 2016YFC1200805], Beijing Municipal Science & Technology Commission [Z161100000116049], National Natural Science Foundation of China [91631110 and U1435222], Beijing Municipal Administration of Hospitals Clinical Medicine Development of Special Funding Support [ZYLX201602NHFPC], Beijing Nova program [Z161100004916101, Z181100006218114], Beijing 215 Project [2015-3-107], China National Grand S&T Special Project [2016ZX10004222-010], and ‘863’ Program [2015AA020108 & 2014AA021501]. WS is supported by the ‘Taishan Scholar’ project of Shandong Province. GW is supported by the President’s International Fellowship Initiative from CAS. JC is supported by CAS Pioneer Hundred Talents Program. GFG is a leading principal investigator of the NSFC Innovative Research Group [81321063]. DL is supported by National Program for Support of Top-notch Young Professionals. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.