Genetic tuning of the novel avian influenza A(H7N9) virus during interspecies transmission, China, 2013

D Wang; L Yang; R Gao; X Zhang; Y Tan; A Wu; W Zhu; J Zhou; S Zou; Xiyan Li; Y Sun; Y Zhang; Y Liu; T Liu; Y Xiong; J Xu; L Chen; Y Weng; X Qi; J Guo; Xiaodan Li; J Dong; W Huang; Y Zhang; L Dong; X Zhao; L Liu; J Lu; Y Lan; H Wei; L Xin; Y Chen; C Xu; T Chen; Y Zhu; T Jiang; Z Feng; W Yang; Y Wang; H Zhu; Y Guan; G F Gao; D Li; J Han; S Wang; G Wu; Y Shu

doi:10.2807/1560-7917.ES2014.19.25.20836

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Genetic tuning of the novel avian influenza A(H7N9) virus during interspecies transmission, China, 2013
D Wang^1,2 , L Yang^1,2 , R Gao¹ , X Zhang³ , Y Tan⁴ , A Wu⁵ , W Zhu¹ , J Zhou¹ , S Zou¹ , Xiyan Li¹ , Y Sun⁶ , Y Zhang⁷ , Y Liu⁸ , T Liu⁹ , Y Xiong¹⁰ , J Xu¹¹ , L Chen¹² , Y Weng¹³ , X Qi¹⁴ , J Guo¹ , Xiaodan Li¹ , J Dong¹ , W Huang¹ , Y Zhang¹ , L Dong¹ , X Zhao¹ , L Liu¹ , J Lu¹ , Y Lan¹ , H Wei¹ , L Xin¹ , Y Chen¹ , C Xu¹ , T Chen¹ , Y Zhu¹ , T Jiang⁵ , Z Feng¹⁵ , W Yang¹⁵ , Y Wang¹⁵ , H Zhu¹⁶ , Y Guan¹⁶ , G F Gao¹⁵ , D Li¹ , J Han¹ , S Wang¹ , G Wu¹ , Y Shu¹
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Affiliations: ¹ 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 ² These authors contributed equally to this work ³ Shanghai Municipal Disease Control and Prevention, Shanghai, China ⁴ Guangxi Center for Disease Control and Prevention, Nanning, China ⁵ Institutes of Biophysics, Chinese Academy of Sciences, Beijing, China ⁶ Anhui Provincial Disease Control and Prevention, Hefei, China ⁷ Zhejiang Provincial Disease Control and Prevention, Hangzhou, China ⁸ Hunan Provincial Disease Control and Prevention, Changsha, China ⁹ Shandong Provincial Disease Control and Prevention, Jinan, China ¹⁰ Jiangxi Provincial Disease Control and Prevention, Nanchang, China ¹¹ Henan Provincial Disease Control and Prevention, Zhengzhou, China ¹² Beijing Municipal Disease Control and Prevention, Beijing, China ¹³ Fujian Provincial Disease Control and Prevention, Fuzhou, China ¹⁴ Jiangsu Provincial Disease Control and Prevention, Nanjing, China ¹⁵ Chinese Center for Disease Control and Prevention, Beijing, China ¹⁶ The University of Hong Kong, Hong Kong SAR, China

Correspondence:
Y Shu
yshu cnic.org.cn
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Citation style for this article: Wang D, Yang L, Gao R, Zhang X, Tan Y, Wu A, Zhu W, Zhou J, Zou S, Li Xiyan, Sun Y, Zhang Y, Liu Y, Liu T, Xiong Y, Xu J, Chen L, Weng Y, Qi X, Guo J, Li Xiaodan, Dong J, Huang W, Zhang Y, Dong L, Zhao X, Liu L, Lu J, Lan Y, Wei H, Xin L, Chen Y, Xu C, Chen T, Zhu Y, Jiang T, Feng Z, Yang W, Wang Y, Zhu H, Guan Y, Gao G F, Li D, Han J, Wang S, Wu G, Shu Y. Genetic tuning of the novel avian influenza A(H7N9) virus during interspecies transmission, China, 2013 . Euro Surveill. 2014;19(25):pii=20836. https://doi.org/10.2807/1560-7917.ES2014.19.25.20836 Received: 28 Jul 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.