title: PB2-588 V promotes the mammalian adaptation of H10N8, H7N9 and H9N2 avian influenza viruses.
abstract: Human infections with avian influenza H7N9 or H10N8 viruses have been reported in China, raising concerns that they might cause human epidemics and pandemics. However, how these viruses adapt to mammalian hosts is unclear. Here we show that besides the commonly recognized viral polymerase subunit PB2 residue 627 K, other residues including 87E, 292 V, 340 K, 588 V, 648 V, and 676 M in PB2 also play critical roles in mammalian adaptation of the H10N8 virus. The avian-origin H10N8, H7N9, and H9N2 viruses harboring PB2-588 V exhibited higher polymerase activity, more efficient replication in mammalian and avian cells, and higher virulence in mice when compared to viruses with PB2-588 A. Analyses of available PB2 sequences showed that the proportion of avian H9N2 or human H7N9 influenza isolates bearing PB2-588 V has increased significantly since 2013. Taken together, our results suggest that the substitution PB2-A588V may be a new strategy for an avian influenza virus to adapt mammalian hosts.
authors.affiliation: National and Local Joint Engineering Laboratory for Medicament of Zoonosis Prevention and Control, College of Veterinary Medicine, South China Agricultural University, Guangzhou, Guangdong Province 510642, People's Republic of China.
authors.forename: Chencheng
authors.initials: C
authors.lastname: Xiao
authors.affiliation: Department of Diagnostic Medicine/Pathobiology, Kansas State University, Manhattan, KS 66502, USA.
authors.forename: Wenjun
authors.initials: W
authors.lastname: Ma
authors.affiliation: National and Local Joint Engineering Laboratory for Medicament of Zoonosis Prevention and Control, College of Veterinary Medicine, South China Agricultural University, Guangzhou, Guangdong Province 510642, People's Republic of China.
authors.forename: Na
authors.initials: N
authors.lastname: Sun
authors.affiliation: National and Local Joint Engineering Laboratory for Medicament of Zoonosis Prevention and Control, College of Veterinary Medicine, South China Agricultural University, Guangzhou, Guangdong Province 510642, People's Republic of China.
authors.forename: Lihong
authors.initials: L
authors.lastname: Huang
authors.affiliation: National and Local Joint Engineering Laboratory for Medicament of Zoonosis Prevention and Control, College of Veterinary Medicine, South China Agricultural University, Guangzhou, Guangdong Province 510642, People's Republic of China.
authors.forename: Yaling
authors.initials: Y
authors.lastname: Li
authors.affiliation: National and Local Joint Engineering Laboratory for Medicament of Zoonosis Prevention and Control, College of Veterinary Medicine, South China Agricultural University, Guangzhou, Guangdong Province 510642, People's Republic of China.
authors.forename: Zhaoyong
authors.initials: Z
authors.lastname: Zeng
authors.affiliation: National and Local Joint Engineering Laboratory for Medicament of Zoonosis Prevention and Control, College of Veterinary Medicine, South China Agricultural University, Guangzhou, Guangdong Province 510642, People's Republic of China.
authors.forename: Yijun
authors.initials: Y
authors.lastname: Wen
authors.affiliation: National and Local Joint Engineering Laboratory for Medicament of Zoonosis Prevention and Control, College of Veterinary Medicine, South China Agricultural University, Guangzhou, Guangdong Province 510642, People's Republic of China.
authors.forename: Zaoyue
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: National and Local Joint Engineering Laboratory for Medicament of Zoonosis Prevention and Control, College of Veterinary Medicine, South China Agricultural University, Guangzhou, Guangdong Province 510642, People's Republic of China.
authors.forename: Huanan
authors.initials: H
authors.lastname: Li
authors.affiliation: National and Local Joint Engineering Laboratory for Medicament of Zoonosis Prevention and Control, College of Veterinary Medicine, South China Agricultural University, Guangzhou, Guangdong Province 510642, People's Republic of China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Li
authors.affiliation: National and Local Joint Engineering Laboratory for Medicament of Zoonosis Prevention and Control, College of Veterinary Medicine, South China Agricultural University, Guangzhou, Guangdong Province 510642, People's Republic of China.
authors.forename: Yuandi
authors.initials: Y
authors.lastname: Yu
authors.affiliation: National and Local Joint Engineering Laboratory for Medicament of Zoonosis Prevention and Control, College of Veterinary Medicine, South China Agricultural University, Guangzhou, Guangdong Province 510642, People's Republic of China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Zheng
authors.affiliation: National and Local Joint Engineering Laboratory for Medicament of Zoonosis Prevention and Control, College of Veterinary Medicine, South China Agricultural University, Guangzhou, Guangdong Province 510642, People's Republic of China.
authors.forename: Shukai
authors.initials: S
authors.lastname: Liu
authors.affiliation: National and Local Joint Engineering Laboratory for Medicament of Zoonosis Prevention and Control, College of Veterinary Medicine, South China Agricultural University, Guangzhou, Guangdong Province 510642, People's Republic of China.
authors.forename: Pingsheng
authors.initials: P
authors.lastname: Hu
authors.affiliation: National and Local Joint Engineering Laboratory for Medicament of Zoonosis Prevention and Control, College of Veterinary Medicine, South China Agricultural University, Guangzhou, Guangdong Province 510642, People's Republic of China.
authors.forename: Xu
authors.initials: X
authors.lastname: Zhang
authors.affiliation: National and Local Joint Engineering Laboratory for Medicament of Zoonosis Prevention and Control, College of Veterinary Medicine, South China Agricultural University, Guangzhou, Guangdong Province 510642, People's Republic of China.
authors.forename: Zhangyong
authors.initials: Z
authors.lastname: Ning
authors.affiliation: National and Local Joint Engineering Laboratory for Medicament of Zoonosis Prevention and Control, College of Veterinary Medicine, South China Agricultural University, Guangzhou, Guangdong Province 510642, People's Republic of China.
authors.forename: Wenbao
authors.initials: W
authors.lastname: Qi
authors.affiliation: National and Local Joint Engineering Laboratory for Medicament of Zoonosis Prevention and Control, College of Veterinary Medicine, South China Agricultural University, Guangzhou, Guangdong Province 510642, People's Republic of China.
authors.forename: Ming
authors.initials: M
authors.lastname: Liao
mesh_terms: D000222:Adaptation, Physiological / Q000502:physiology*; D019943:Amino Acid Substitution / Q000235:genetics; D000818:Animals; D001717:Birds; D002645:Chickens; D002681:China; D004285:Dogs; D005260:Female; D057809:HEK293 Cells; D006801:Humans; D065926:Influenza A Virus, H10N8 Subtype / Q000472:pathogenicity*; D064766:Influenza A Virus, H7N9 Subtype / Q000472:pathogenicity*; D053127:Influenza A Virus, H9N2 Subtype / Q000472:pathogenicity*; D005585:Influenza in Birds / Q000821:virology; D007251:Influenza, Human / Q000821:virology; D061985:Madin Darby Canine Kidney Cells; D008322:Mammals / Q000821:virology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009976:Orthomyxoviridae Infections / Q000821:virology; D012324:RNA-Dependent RNA Polymerase / Q000235:genetics; D014764:Viral Proteins / Q000235:genetics; D014774:Virulence / Q000235:genetics; D014779:Virus Replication / Q000235:genetics
chemical_list: D014764:Viral Proteins; D012324:RNA-Dependent RNA Polymerase