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

Phylogenomic analysis unravels evolution of yellow fever virus within hosts.

Chen C1,2, Jiang D1,2, Ni M3, Li J4, Chen Z1,2,5, Liu J6, Ye H7, Wong G4, Li W4, Zhang Y1,2, Wang B1,2, Bi Y4, Chen D1,2, Zhang P7, Zhao X1,2, Kong Y1,2, Shi W8, Du P1,2, Xiao G9, Ma J4, Gao GF4,10,11, Cui J9, Zhang F1,2,5, Liu W4,10, Bo X3, Li A1,2, Zeng H1,2, Liu D4,9,10.

Author information

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


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.

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