title: The origin of novel avian influenza A (H7N9) and mutation dynamics for its human-to-human transmissible capacity.
abstract: In February 2013, H7N9 (A/H7N9/2013_China), a novel avian influenza virus, broke out in eastern China and caused human death. It is a global priority to discover its origin and the point in time at which it will become transmittable between humans. We present here an interdisciplinary method to track the origin of H7N9 virus in China and to establish an evolutionary dynamics model for its human-to-human transmission via mutations. After comparing influenza viruses from China since 1983, we established an A/H7N9/2013_China virus evolutionary phylogenetic tree and found that the human instances of virus infection were of avian origin and clustered into an independent line. Comparing hemagglutinin (HA) and neuraminidase (NA) gene sequences of A/H7N9/2013_China viruses with all human-to-human, avian, and swine influenza viruses in China in the past 30 years, we found that A/H7N9/2013_China viruses originated from Baer's Pochard H7N1 virus of Hu Nan Province 2010 (HA gene, EPI: 370846, similarity with H7N9 is 95.5%) and duck influenza viruses of Nanchang city 2000 (NA gene, EPI: 387555, similarity with H7N9 is 97%) through genetic re-assortment. HA and NA gene sequence comparison indicated that A/H7N9/2013_China virus was not similar to human-to-human transmittable influenza viruses. To simulate the evolution dynamics required for human-to-human transmission mutations of H7N9 virus, we employed the Markov model. The result of this calculation indicated that the virus would acquire properties for human-to-human transmission in 11.3 years (95% confidence interval (CI): 11.2-11.3, HA gene).
authors.affiliation: Department of Computational Mathematics and Bio-Statistics, Metabolomics and Multidisciplinary Laboratory for Trauma Research, Institute for Emergency and Disaster Medicine, Sichuan Provincial People's Hospital, Sichuan Academy of Medical Sciences, Chengdu, Sichuan Province, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Peng
authors.affiliation: Department of Computational Mathematics and Bio-Statistics, Metabolomics and Multidisciplinary Laboratory for Trauma Research, Institute for Emergency and Disaster Medicine, Sichuan Provincial People's Hospital, Sichuan Academy of Medical Sciences, Chengdu, Sichuan Province, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Yang
authors.affiliation: Department of Computational Mathematics and Bio-Statistics, Metabolomics and Multidisciplinary Laboratory for Trauma Research, Institute for Emergency and Disaster Medicine, Sichuan Provincial People's Hospital, Sichuan Academy of Medical Sciences, Chengdu, Sichuan Province, China; Emergency Medicine Center, Sichuan Provincial People's Hospital, Sichuan Academy of Medical Sciences, Chengdu, Sichuan Province, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Jiang
authors.affiliation: Department of Computational Mathematics and Bio-Statistics, Metabolomics and Multidisciplinary Laboratory for Trauma Research, Institute for Emergency and Disaster Medicine, Sichuan Provincial People's Hospital, Sichuan Academy of Medical Sciences, Chengdu, Sichuan Province, China.
authors.forename: Yi-xiao
authors.initials: YX
authors.lastname: Lin
authors.affiliation: Department of Computational Mathematics and Bio-Statistics, Metabolomics and Multidisciplinary Laboratory for Trauma Research, Institute for Emergency and Disaster Medicine, Sichuan Provincial People's Hospital, Sichuan Academy of Medical Sciences, Chengdu, Sichuan Province, China.
authors.forename: Charles Damien
authors.initials: CD
authors.lastname: Lu
authors.affiliation: Department of Computational Mathematics and Bio-Statistics, Metabolomics and Multidisciplinary Laboratory for Trauma Research, Institute for Emergency and Disaster Medicine, Sichuan Provincial People's Hospital, Sichuan Academy of Medical Sciences, Chengdu, Sichuan Province, China.
authors.forename: Ya-wei
authors.initials: YW
authors.lastname: Xu
authors.affiliation: Department of Computational Mathematics and Bio-Statistics, Metabolomics and Multidisciplinary Laboratory for Trauma Research, Institute for Emergency and Disaster Medicine, Sichuan Provincial People's Hospital, Sichuan Academy of Medical Sciences, Chengdu, Sichuan Province, China; Emergency Medicine Center, Sichuan Provincial People's Hospital, Sichuan Academy of Medical Sciences, Chengdu, Sichuan Province, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Zeng
mesh_terms: D000818:Animals; D002681:China; D004372:Ducks / Q000821:virology; D019143:Evolution, Molecular; D005814:Genes, Viral; D006801:Humans; D064766:Influenza A Virus, H7N9 Subtype / Q000235:genetics*; D005585:Influenza in Birds / Q000821:virology*; D007251:Influenza, Human / Q000635:transmission / Q000821:virology*; D008390:Markov Chains; D008957:Models, Genetic; D059645:Mutation Rate; D010802:Phylogeny; D012689:Sequence Homology, Nucleic Acid; D015047:Zoonoses