[Source: The Lancet, full text: (LINK). Abstract, edited.]
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The Lancet, Early Online Publication, 1 May 2013
doi:10.1016/S0140-6736(13)60938-1
Origin and diversity of novel avian influenza A H7N9 viruses causing human infection: phylogenetic, structural, and coalescent analyses
Original Text
Di Liu PhD a b *, Weifeng Shi PhD c d *, Yi Shi PhD a e, Dayan Wang PhD f, Haixia Xiao g, Wei Li MSc b, Yuhai Bi PhD a, Ying Wu PhD a, Xianbin Li BSc h i, Prof Jinghua Yan PhD a, Prof Wenjun Liu PhD a, Prof Guoping Zhao PhD j, Prof Weizhong Yang MD k, Prof Yu Wang MD k, Prof Juncai Ma PhD b, Prof Yuelong Shu PhD f ?, Prof Fumin Lei PhD d ?, Prof George F Gao DPhil a e f i k ?
Summary
Background
On March 30, 2013, a novel avian influenza A H7N9 virus that infects human beings was identified. This virus had been detected in six provinces and municipal cities in China as of April 18, 2013. We correlated genomic sequences from avian influenza viruses with ecological information and did phylogenetic and coalescent analyses to extrapolate the potential origins of the virus and possible routes of reassortment events.
Methods
We downloaded H7N9 virus genome sequences from the Global Initiative on Sharing Avian Influenza Data (GISAID) database and public sequences used from the Influenza Virus Resource. We constructed phylogenetic trees and did 1000 bootstrap replicates for each tree. Two rounds of phylogenetic analyses were done. We used at least 100 closely related sequences for each gene to infer the overall topology, removed suspicious sequences from the trees, and focused on the closest clades to the novel H7N9 viruses. We compared our tree topologies with those from a bayesian evolutionary analysis by sampling trees (BEAST) analysis. We used the bayesian Markov chain Monte Carlo method to jointly estimate phylogenies, divergence times, and other evolutionary parameters for all eight gene fragments. We used sequence alignment and homology-modelling methods to study specific mutations regarding phenotypes, specifically addressing the human receptor binding properties.
Findings
The novel avian influenza A H7N9 virus originated from multiple reassortment events. The HA gene might have originated from avian influenza viruses of duck origin, and the NA gene might have transferred from migratory birds infected with avian influenza viruses along the east Asian flyway. The six internal genes of this virus probably originated from two different groups of H9N2 avian influenza viruses, which were isolated from chickens. Detailed analyses also showed that ducks and chickens probably acted as the intermediate hosts leading to the emergence of this virulent H7N9 virus. Genotypic and potential phenotypic differences imply that the isolates causing this outbreak form two separate subclades.
Interpretation
The novel avian influenza A H7N9 virus might have evolved from at least four origins. Diversity among isolates implies that the H7N9 virus has evolved into at least two different lineages. Unknown intermediate hosts involved might be implicated, extensive global surveillance is needed, and domestic-poultry-to-person transmission should be closely watched in the future.
Funding
China Ministry of Science and Technology Project 973, National Natural Science Foundation of China, China Health and Family Planning Commission, Chinese Academy of Sciences.
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a CAS Key Laboratory of Pathogenic Microbiology and Immunology, Chinese Academy of Sciences, Beijing, China; b Network Information Center, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China; c School of Basic Medical Sciences, Taishan Medical College, Shandong Province, China; d Key Laboratory of Zoological Systematics and Evolution, Institute of Zoology, Chinese Academy of Sciences, Beijing, China; e Beijing Institutes of Life Science, Chinese Academy of Sciences, Beijing, China; f National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China; g Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, Tianjin, China; h Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China; i University of Chinese Academy of Sciences, Beijing, China; j Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China; k Chinese Center for Disease Control and Prevention, Beijing, China
Corresponding Author Information Correspondence to: Prof George F Gao, Institute of Microbiology, Chinese Academy of Sciences, 1 West Beichen Road, Chaoyang, Beijing 100101, China
* These authors contributed equally to this work
? These authors contributed equally to this work
-doi:10.1016/S0140-6736(13)60938-1
Origin and diversity of novel avian influenza A H7N9 viruses causing human infection: phylogenetic, structural, and coalescent analyses
Original Text
Di Liu PhD a b *, Weifeng Shi PhD c d *, Yi Shi PhD a e, Dayan Wang PhD f, Haixia Xiao g, Wei Li MSc b, Yuhai Bi PhD a, Ying Wu PhD a, Xianbin Li BSc h i, Prof Jinghua Yan PhD a, Prof Wenjun Liu PhD a, Prof Guoping Zhao PhD j, Prof Weizhong Yang MD k, Prof Yu Wang MD k, Prof Juncai Ma PhD b, Prof Yuelong Shu PhD f ?, Prof Fumin Lei PhD d ?, Prof George F Gao DPhil a e f i k ?
Summary
Background
On March 30, 2013, a novel avian influenza A H7N9 virus that infects human beings was identified. This virus had been detected in six provinces and municipal cities in China as of April 18, 2013. We correlated genomic sequences from avian influenza viruses with ecological information and did phylogenetic and coalescent analyses to extrapolate the potential origins of the virus and possible routes of reassortment events.
Methods
We downloaded H7N9 virus genome sequences from the Global Initiative on Sharing Avian Influenza Data (GISAID) database and public sequences used from the Influenza Virus Resource. We constructed phylogenetic trees and did 1000 bootstrap replicates for each tree. Two rounds of phylogenetic analyses were done. We used at least 100 closely related sequences for each gene to infer the overall topology, removed suspicious sequences from the trees, and focused on the closest clades to the novel H7N9 viruses. We compared our tree topologies with those from a bayesian evolutionary analysis by sampling trees (BEAST) analysis. We used the bayesian Markov chain Monte Carlo method to jointly estimate phylogenies, divergence times, and other evolutionary parameters for all eight gene fragments. We used sequence alignment and homology-modelling methods to study specific mutations regarding phenotypes, specifically addressing the human receptor binding properties.
Findings
The novel avian influenza A H7N9 virus originated from multiple reassortment events. The HA gene might have originated from avian influenza viruses of duck origin, and the NA gene might have transferred from migratory birds infected with avian influenza viruses along the east Asian flyway. The six internal genes of this virus probably originated from two different groups of H9N2 avian influenza viruses, which were isolated from chickens. Detailed analyses also showed that ducks and chickens probably acted as the intermediate hosts leading to the emergence of this virulent H7N9 virus. Genotypic and potential phenotypic differences imply that the isolates causing this outbreak form two separate subclades.
Interpretation
The novel avian influenza A H7N9 virus might have evolved from at least four origins. Diversity among isolates implies that the H7N9 virus has evolved into at least two different lineages. Unknown intermediate hosts involved might be implicated, extensive global surveillance is needed, and domestic-poultry-to-person transmission should be closely watched in the future.
Funding
China Ministry of Science and Technology Project 973, National Natural Science Foundation of China, China Health and Family Planning Commission, Chinese Academy of Sciences.
____________
a CAS Key Laboratory of Pathogenic Microbiology and Immunology, Chinese Academy of Sciences, Beijing, China; b Network Information Center, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China; c School of Basic Medical Sciences, Taishan Medical College, Shandong Province, China; d Key Laboratory of Zoological Systematics and Evolution, Institute of Zoology, Chinese Academy of Sciences, Beijing, China; e Beijing Institutes of Life Science, Chinese Academy of Sciences, Beijing, China; f National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China; g Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, Tianjin, China; h Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China; i University of Chinese Academy of Sciences, Beijing, China; j Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China; k Chinese Center for Disease Control and Prevention, Beijing, China
Corresponding Author Information Correspondence to: Prof George F Gao, Institute of Microbiology, Chinese Academy of Sciences, 1 West Beichen Road, Chaoyang, Beijing 100101, China
* These authors contributed equally to this work
? These authors contributed equally to this work
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