title: Genetic tuning of the novel avian influenza A(H7N9) virus during interspecies transmission, China, 2013.
abstract: A novel avian influenza A(H7N9) virus causing human infection emerged in February 2013 in China. To elucidate the mechanism of interspecies transmission, we compared the signature amino acids of avian influenza A(H7N9) viruses from human and non-human hosts and analysed the reassortants of 146 influenza A(H7N9) viruses with full genome sequences. We propose a genetic tuning procedure with continuous amino acid substitutions and reassorting that mediates host adaptation and interspecies transmission. When the early influenza A(H7N9) virus, containing ancestor haemagglutinin (HA) and neuraminidase (NA) genes similar to A/Shanghai/05 virus, circulated in waterfowl and transmitted to terrestrial poultry, it acquired an NA stalk deletion at amino acid positions 69 to 73. Then, receptor binding preference was tuned to increase the affinity to human-like receptors through HA G186V and Q226L mutations in terrestrial poultry. Additional mammalian adaptations such as PB2 E627K were selected in humans. The continual reassortation between H7N9 and H9N2 viruses resulted in multiple genotypes for further host adaptation. When we analysed a potential association of mutations and reassortants with clinical outcome, only the PB2 E627K mutation slightly increased the case fatality rate. Genetic tuning may create opportunities for further adaptation of influenza A(H7N9) and its potential to cause a pandemic.
authors.affiliation: National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Key Laboratory for Medical Virology, National Health and Family Planning Commission, Beijing, China.
authors.forename: D
authors.initials: D
authors.lastname: Wang
authors.forename: L
authors.initials: L
authors.lastname: Yang
authors.forename: R
authors.initials: R
authors.lastname: Gao
authors.forename: X
authors.initials: X
authors.lastname: Zhang
authors.forename: Y
authors.initials: Y
authors.lastname: Tan
authors.forename: A
authors.initials: A
authors.lastname: Wu
authors.forename: W
authors.initials: W
authors.lastname: Zhu
authors.forename: J
authors.initials: J
authors.lastname: Zhou
authors.forename: S
authors.initials: S
authors.lastname: Zou
authors.forename: Xiyan
authors.initials: X
authors.lastname: Li
authors.forename: Y
authors.initials: Y
authors.lastname: Sun
authors.forename: Y
authors.initials: Y
authors.lastname: Zhang
authors.forename: Y
authors.initials: Y
authors.lastname: Liu
authors.forename: T
authors.initials: T
authors.lastname: Liu
authors.forename: Y
authors.initials: Y
authors.lastname: Xiong
authors.forename: J
authors.initials: J
authors.lastname: Xu
authors.forename: L
authors.initials: L
authors.lastname: Chen
authors.forename: Y
authors.initials: Y
authors.lastname: Weng
authors.forename: X
authors.initials: X
authors.lastname: Qi
authors.forename: J
authors.initials: J
authors.lastname: Guo
authors.forename: Xiaodan
authors.initials: X
authors.lastname: Li
authors.forename: J
authors.initials: J
authors.lastname: Dong
authors.forename: W
authors.initials: W
authors.lastname: Huang
authors.forename: Y
authors.initials: Y
authors.lastname: Zhang
authors.forename: L
authors.initials: L
authors.lastname: Dong
authors.forename: X
authors.initials: X
authors.lastname: Zhao
authors.forename: L
authors.initials: L
authors.lastname: Liu
authors.forename: J
authors.initials: J
authors.lastname: Lu
authors.forename: Y
authors.initials: Y
authors.lastname: Lan
authors.forename: H
authors.initials: H
authors.lastname: Wei
authors.forename: L
authors.initials: L
authors.lastname: Xin
authors.forename: Y
authors.initials: Y
authors.lastname: Chen
authors.forename: C
authors.initials: C
authors.lastname: Xu
authors.forename: T
authors.initials: T
authors.lastname: Chen
authors.forename: Y
authors.initials: Y
authors.lastname: Zhu
authors.forename: T
authors.initials: T
authors.lastname: Jiang
authors.forename: Z
authors.initials: Z
authors.lastname: Feng
authors.forename: W
authors.initials: W
authors.lastname: Yang
authors.forename: Y
authors.initials: Y
authors.lastname: Wang
authors.forename: H
authors.initials: H
authors.lastname: Zhu
authors.forename: Y
authors.initials: Y
authors.lastname: Guan
authors.forename: G F
authors.initials: GF
authors.lastname: Gao
authors.forename: D
authors.initials: D
authors.lastname: Li
authors.forename: J
authors.initials: J
authors.lastname: Han
authors.forename: S
authors.initials: S
authors.lastname: Wang
authors.forename: G
authors.initials: G
authors.lastname: Wu
authors.forename: Y
authors.initials: Y
authors.lastname: Shu
mesh_terms: D019943:Amino Acid Substitution; D000818:Animals; D001483:Base Sequence; D002681:China; D016679:Genome, Viral / Q000235:genetics*; D006801:Humans; D064766:Influenza A Virus, H7N9 Subtype / Q000235:genetics* / Q000302:isolation & purification*; D005585:Influenza in Birds / Q000235:genetics / Q000635:transmission / Q000821:virology*; D007251:Influenza, Human / Q000235:genetics / Q000635:transmission / Q000821:virology*; D009439:Neuraminidase / Q000235:genetics; D010802:Phylogeny; D011200:Poultry; D011201:Poultry Diseases / Q000235:genetics / Q000821:virology*; D017422:Sequence Analysis, DNA; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D014764:Viral Proteins; D009439:Neuraminidase