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Nat Microbiol. 2016 Sep 5;1(11):16151. doi: 10.1038/nmicrobiol.2016.151.

Intra-host dynamics of Ebola virus during 2014.

Ni M1, Chen C2,3, Qian J4, Xiao HX5,6, Shi WF7, Luo Y8, Wang HY2, Li Z1, Wu J5, Xu PS9, Chen SH1, Wong G5, Bi Y5,10, Xia ZP4, Li W11, Lu HJ4, Ma J11, Tong YG12, Zeng H2,3, Wang SQ1, Gao GF5,10,13, Bo XC1, Liu D5,11.

Author information

1
Beijing Institute of Radiation Medicine, Beijing 100850, China.
2
Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing 100102, China.
3
Beijing Key Laboratory of Emerging Infectious Diseases, Beijing 100102, China.
4
Key Laboratory of Jilin Province for Zoonosis Prevention and Control, Changchun 130122, China.
5
CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.
6
Laboratory of Protein Engineering and Vaccines, Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, Tianjin 300308, China.
7
Institute of Pathogen Biology, Taishan Medical College, Taian 271016, China.
8
Wellcome Trust Sanger Institute, Cambridge CB10 1SA, UK.
9
Zhiyuan Medical Inspection Institute, Zhejiang 310009, China.
10
Shenzhen Key Laboratory of Pathogen and Immunity, Shenzhen Third People's Hospital, Shenzhen 518112, China.
11
Network Information Center, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.
12
State Key Laboratory of Pathogen and Biosecurity, Beijing 100071, China.
13
National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention (China CDC), Beijing 102206, China.

Abstract

Since 2013, West Africa has encountered the largest Ebola virus (EBOV) disease outbreak on record, and Sierra Leone is the worst-affected country, with nearly half of the infections. By means of next-generation sequencing and phylogeographic analysis, the epidemiology and transmission of EBOV have been well elucidated. However, the intra-host dynamics that mainly reflect viral-host interactions still need to be studied. Here, we show a total of 710 intra-host single nucleotide variations (iSNVs) from deep-sequenced samples from EBOV-infected patients, through a well-tailored bioinformatics pipeline. We present a comprehensive distribution of iSNVs during this outbreak and along the EBOV genome. Analyses of iSNV and its allele frequency reveal that VP40 is the most conserved gene during this outbreak, and thus it would be an ideal therapeutic target. In the co-occurring iSNV network, varied iSNV sites present different selection features. Intriguingly, the T-to-C substitutions at the 3'-UTR of the nucleoprotein (NP; positions 3008 and 3011), observed in many patients, result in the upregulation of the transcription of NP through an Ebola mini-genome reporting system. Additionally, no iSNV enrichment within B-cell epitopes of GP has been observed.

PMID:
27595345
DOI:
10.1038/nmicrobiol.2016.151
[Indexed for MEDLINE]

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