title: Adaptive amino acid substitutions enhance the virulence of an H7N7 avian influenza virus isolated from wild waterfowl in mice.
abstract: Although H7N7 AIVs primarily circulate in wild waterfowl, documented cases of human infection with H7N7 viruses suggest they may pose a pandemic threat. Here, we generated mouse-adapted variants of a wild waterfowl-origin H7N7 virus to identify adaptive changes that confer enhanced virulence in mammals. The mouse lethal doses (MLD50) of the adapted variants were reduced >5000-fold compared to the parental virus. Mouse-adapted variants viruses displayed enhanced replication in vitro and in vivo, and acquired the ability to replicate in extrapulmonary tissues. These observations suggest that enhanced growth characteristics and modified cell tropism may increase the virulence of H7N7 AIVs in mice. Genomic analysis of the adapted variant viruses revealed amino acid changes in the PB2 (E627K), PB1 (R118I), PA (L550M), HA (G214R), and NA (S372N) proteins. Our results suggest that these amino acid substitutions collaboratively enhance the ability of H7N7 virus to replicate and cause severe disease in mammals.
authors.affiliation: College of Wildlife Resources, Northeast Forestry University, Harbin 150040, People's Republic of China; Liaoning Medical University, Jinzhou 121001, People's Republic of China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Chen
authors.affiliation: Key Laboratory of Jilin Province for Zoonosis Prevention and Control, Military Veterinary Research Institute, Academy of Military Medical Sciences, Changchun 130122, People's Republic of China; Institute of Laboratory Animal Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100021, People's Republic of China.
authors.forename: Zhijun
authors.initials: Z
authors.lastname: Yu
authors.affiliation: Key Laboratory of Jilin Province for Zoonosis Prevention and Control, Military Veterinary Research Institute, Academy of Military Medical Sciences, Changchun 130122, People's Republic of China.
authors.forename: Weiyang
authors.initials: W
authors.lastname: Sun
authors.affiliation: Key Laboratory of Jilin Province for Zoonosis Prevention and Control, Military Veterinary Research Institute, Academy of Military Medical Sciences, Changchun 130122, People's Republic of China; Changchun Institute of Biological Products, Changchun 130122, People's Republic of China.
authors.forename: Xue
authors.initials: X
authors.lastname: Li
authors.affiliation: College of Wildlife Resources, Northeast Forestry University, Harbin 150040, People's Republic of China.
authors.forename: Hongliang
authors.initials: H
authors.lastname: Chai
authors.affiliation: Key Laboratory of Jilin Province for Zoonosis Prevention and Control, Military Veterinary Research Institute, Academy of Military Medical Sciences, Changchun 130122, People's Republic of China.
authors.forename: Xiaolong
authors.initials: X
authors.lastname: Gao
authors.affiliation: Key Laboratory of Jilin Province for Zoonosis Prevention and Control, Military Veterinary Research Institute, Academy of Military Medical Sciences, Changchun 130122, People's Republic of China.
authors.forename: Jiao
authors.initials: J
authors.lastname: Guo
authors.affiliation: Key Laboratory of Jilin Province for Zoonosis Prevention and Control, Military Veterinary Research Institute, Academy of Military Medical Sciences, Changchun 130122, People's Republic of China; Institute of Laboratory Animal Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100021, People's Republic of China.
authors.forename: Kun
authors.initials: K
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Jilin Province for Zoonosis Prevention and Control, Military Veterinary Research Institute, Academy of Military Medical Sciences, Changchun 130122, People's Republic of China.
authors.forename: Na
authors.initials: N
authors.lastname: Feng
authors.affiliation: Key Laboratory of Jilin Province for Zoonosis Prevention and Control, Military Veterinary Research Institute, Academy of Military Medical Sciences, Changchun 130122, People's Republic of China.
authors.forename: Xuexing
authors.initials: X
authors.lastname: Zheng
authors.affiliation: Key Laboratory of Jilin Province for Zoonosis Prevention and Control, Military Veterinary Research Institute, Academy of Military Medical Sciences, Changchun 130122, People's Republic of China.
authors.forename: Hualei
authors.initials: H
authors.lastname: Wang
authors.affiliation: Key Laboratory of Jilin Province for Zoonosis Prevention and Control, Military Veterinary Research Institute, Academy of Military Medical Sciences, Changchun 130122, People's Republic of China; Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou 225009, People's Republic of China.
authors.forename: Yongkun
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Institute of Laboratory Animal Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100021, People's Republic of China.
authors.forename: Chuan
authors.initials: C
authors.lastname: Qin
authors.affiliation: Key Laboratory of Jilin Province for Zoonosis Prevention and Control, Military Veterinary Research Institute, Academy of Military Medical Sciences, Changchun 130122, People's Republic of China.
authors.forename: Geng
authors.initials: G
authors.lastname: Huang
authors.affiliation: Key Laboratory of Jilin Province for Zoonosis Prevention and Control, Military Veterinary Research Institute, Academy of Military Medical Sciences, Changchun 130122, People's Republic of China.
authors.forename: Songtao
authors.initials: S
authors.lastname: Yang
authors.affiliation: Key Laboratory of Jilin Province for Zoonosis Prevention and Control, Military Veterinary Research Institute, Academy of Military Medical Sciences, Changchun 130122, People's Republic of China; Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou 225009, People's Republic of China.
authors.forename: Jun
authors.initials: J
authors.lastname: Qian
authors.affiliation: Key Laboratory of Jilin Province for Zoonosis Prevention and Control, Military Veterinary Research Institute, Academy of Military Medical Sciences, Changchun 130122, People's Republic of China; Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou 225009, People's Republic of China.
authors.forename: Yuwei
authors.initials: Y
authors.lastname: Gao
authors.affiliation: Key Laboratory of Jilin Province for Zoonosis Prevention and Control, Military Veterinary Research Institute, Academy of Military Medical Sciences, Changchun 130122, People's Republic of China; Institute of Laboratory Animal Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100021, People's Republic of China; Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou 225009, People's Republic of China. Electronic address: xiaxianzhu1939@126.com.
authors.forename: Xianzhu
authors.initials: X
authors.lastname: Xia
authors.affiliation: Key Laboratory of Jilin Province for Zoonosis Prevention and Control, Military Veterinary Research Institute, Academy of Military Medical Sciences, Changchun 130122, People's Republic of China; Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou 225009, People's Republic of China. Electronic address: wgcha@163.com.
authors.forename: Tiecheng
authors.initials: T
authors.lastname: Wang
authors.affiliation: College of Wildlife Resources, Northeast Forestry University, Harbin 150040, People's Republic of China. Electronic address: yuping_hua@126.com.
authors.forename: Yuping
authors.initials: Y
authors.lastname: Hua
mesh_terms: D019943:Amino Acid Substitution; D000818:Animals; D046090:Anseriformes / Q000821:virology*; D006801:Humans; D053126:Influenza A Virus, H7N7 Subtype / Q000235:genetics* / Q000472:pathogenicity*; D009980:Influenza A virus / Q000235:genetics; D005585:Influenza in Birds / Q000821:virology*; D051379:Mice; D014764:Viral Proteins / Q000235:genetics; D014774:Virulence / Q000235:genetics
chemical_list: D014764:Viral Proteins
keywords: Adaptation; Avian influenza virus; H7N7; Mice; Wild waterfowl