Intra-host dynamics of Ebola virus during 2014.
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.
Beijing Institute of Radiation Medicine, Beijing 100850, China.
Ming
M
Ni
Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing 100102, China.|Beijing Key Laboratory of Emerging Infectious Diseases, Beijing 100102, China.
Chen
C
Chen
Key Laboratory of Jilin Province for Zoonosis Prevention and Control, Changchun 130122, China.
Jun
J
Qian
CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.|Laboratory of Protein Engineering and Vaccines, Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, Tianjin 300308, China.
Hai-Xia
HX
Xiao
Institute of Pathogen Biology, Taishan Medical College, Taian 271016, China.
Wei-Feng
WF
Shi
Wellcome Trust Sanger Institute, Cambridge CB10 1SA, UK.
Yang
Y
Luo
Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing 100102, China.
Hai-Yin
HY
Wang
Beijing Institute of Radiation Medicine, Beijing 100850, China.
Zhen
Z
Li
CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.
Jun
J
Wu
Zhiyuan Medical Inspection Institute, Zhejiang 310009, China.
Pei-Song
PS
Xu
Beijing Institute of Radiation Medicine, Beijing 100850, China.
Su-Hong
SH
Chen
CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.
Gary
G
Wong
CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.|Shenzhen Key Laboratory of Pathogen and Immunity, Shenzhen Third People's Hospital, Shenzhen 518112, China.
Yuhai
Y
Bi
Key Laboratory of Jilin Province for Zoonosis Prevention and Control, Changchun 130122, China.
Zhi-Ping
ZP
Xia
Network Information Center, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.
Wei
W
Li
Key Laboratory of Jilin Province for Zoonosis Prevention and Control, Changchun 130122, China.
Hui-Jun
HJ
Lu
Network Information Center, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.
Juncai
J
Ma
State Key Laboratory of Pathogen and Biosecurity, Beijing 100071, China.
Yi-Gang
YG
Tong
Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing 100102, China.|Beijing Key Laboratory of Emerging Infectious Diseases, Beijing 100102, China.
Hui
H
Zeng
Beijing Institute of Radiation Medicine, Beijing 100850, China.
Sheng-Qi
SQ
Wang
CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.|Shenzhen Key Laboratory of Pathogen and Immunity, Shenzhen Third People's Hospital, Shenzhen 518112, China.|National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention (China CDC), Beijing 102206, China.
George F
GF
Gao
Beijing Institute of Radiation Medicine, Beijing 100850, China.
Xiao-Chen
XC
Bo
CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.|Network Information Center, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.
Di
http://orcid.org/0000-0003-3693-2726
D
Liu
D000483:Alleles; D029043:Ebolavirus / Q000235:genetics / Q000502:physiology*; D018985:Epitopes, B-Lymphocyte / Q000235:genetics; D014644:Genetic Variation; D016679:Genome, Viral; D019142:Hemorrhagic Fever, Ebola / Q000453:epidemiology / Q000628:therapy / Q000821:virology*; D059014:High-Throughput Nucleotide Sequencing; D054884:Host-Pathogen Interactions; D006801:Humans; D009698:Nucleoproteins / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D000074704:Quasispecies / Q000235:genetics; D014763:Viral Matrix Proteins / Q000235:genetics
D018985:Epitopes, B-Lymphocyte; D009698:Nucleoproteins; C080981:VP40 protein, virus; D014763:Viral Matrix Proteins