title: Dual E627K and D701N mutations in the PB2 protein of A(H7N9) influenza virus increased its virulence in mammalian models.
abstract: The ongoing avian H7N9 influenza outbreaks in China have caused significant human fatal cases and the virus is becoming established in poultry. Mutations with potential to increase mammalian adaptation have occurred in the polymerase basic protein 2 (PB2) and other viral genes. Here we found that dual 627K and 701N mutations could readily occur during transmission of the virus among ferrets via direct physical contact, and these mutations conferred higher polymerase activity and improved viral replication in mammalian cells, and enhanced virulence in mice. Special attention needs to be paid to patients with such mutations, as these may serve as an indicator of higher virus replication and increased pathogenicity.
authors.affiliation: National Institute for Viral Disease Control and Prevention, Chinese Centre for Disease Control and Prevention, Key Laboratory for Medical Virology, National Health and Family Planning Commission, Beijing.|Joint Influenza Research Centre, Shantou University Medical College, Shantou, Guangdong.|State Key Laboratory of Emerging Infectious Diseases/Centre of Influenza Research, School of Public Health, The University of Hong Kong, Hong Kong SAR.
authors.forename: Wenfei
authors.initials: W
authors.lastname: Zhu
authors.affiliation: Joint Influenza Research Centre, Shantou University Medical College, Shantou, Guangdong.
authors.forename: Long
authors.initials: L
authors.lastname: Li
authors.affiliation: Joint Influenza Research Centre, Shantou University Medical College, Shantou, Guangdong.
authors.forename: Zhigang
authors.initials: Z
authors.lastname: Yan
authors.affiliation: Joint Influenza Research Centre, Shantou University Medical College, Shantou, Guangdong.|State Key Laboratory of Emerging Infectious Diseases/Centre of Influenza Research, School of Public Health, The University of Hong Kong, Hong Kong SAR.
authors.forename: Tanhuan
authors.initials: T
authors.lastname: Gan
authors.affiliation: Joint Influenza Research Centre, Shantou University Medical College, Shantou, Guangdong.|State Key Laboratory of Emerging Infectious Diseases/Centre of Influenza Research, School of Public Health, The University of Hong Kong, Hong Kong SAR.
authors.forename: Lifeng
authors.initials: L
authors.lastname: Li
authors.affiliation: Joint Influenza Research Centre, Shantou University Medical College, Shantou, Guangdong.|State Key Laboratory of Emerging Infectious Diseases/Centre of Influenza Research, School of Public Health, The University of Hong Kong, Hong Kong SAR.
authors.forename: Rirong
authors.initials: R
authors.lastname: Chen
authors.affiliation: Joint Influenza Research Centre, Shantou University Medical College, Shantou, Guangdong.
authors.forename: Ruidong
authors.initials: R
authors.lastname: Chen
authors.affiliation: Joint Influenza Research Centre, Shantou University Medical College, Shantou, Guangdong.|State Key Laboratory of Emerging Infectious Diseases/Centre of Influenza Research, School of Public Health, The University of Hong Kong, Hong Kong SAR.
authors.forename: Zuoyi
authors.initials: Z
authors.lastname: Zheng
authors.affiliation: Joint Influenza Research Centre, Shantou University Medical College, Shantou, Guangdong.
authors.forename: Wenshan
authors.initials: W
authors.lastname: Hong
authors.affiliation: Joint Influenza Research Centre, Shantou University Medical College, Shantou, Guangdong.|State Key Laboratory of Emerging Infectious Diseases/Centre of Influenza Research, School of Public Health, The University of Hong Kong, Hong Kong SAR.
authors.forename: Jia
authors.initials: J
authors.lastname: Wang
authors.affiliation: Joint Influenza Research Centre, Shantou University Medical College, Shantou, Guangdong.|State Key Laboratory of Emerging Infectious Diseases/Centre of Influenza Research, School of Public Health, The University of Hong Kong, Hong Kong SAR.
authors.forename: David K
authors.initials: DK
authors.lastname: Smith
authors.affiliation: Joint Influenza Research Centre, Shantou University Medical College, Shantou, Guangdong.|State Key Laboratory of Emerging Infectious Diseases/Centre of Influenza Research, School of Public Health, The University of Hong Kong, Hong Kong SAR.
authors.forename: Yi
authors.initials: Y
authors.lastname: Guan
authors.affiliation: Joint Influenza Research Centre, Shantou University Medical College, Shantou, Guangdong.|State Key Laboratory of Emerging Infectious Diseases/Centre of Influenza Research, School of Public Health, The University of Hong Kong, Hong Kong SAR.
authors.forename: Huachen
authors.initials: H
authors.lastname: Zhu
authors.affiliation: National Institute for Viral Disease Control and Prevention, Chinese Centre for Disease Control and Prevention, Key Laboratory for Medical Virology, National Health and Family Planning Commission, Beijing.
authors.forename: Yuelong
authors.initials: Y
authors.lastname: Shu
mesh_terms: D000818:Animals; D003062:Codon; D004195:Disease Models, Animal; D004789:Enzyme Activation; D005289:Ferrets; D006801:Humans; D064766:Influenza A Virus, H7N9 Subtype / Q000472:pathogenicity* / Q000502:physiology*; D051379:Mice; D009154:Mutation; D009976:Orthomyxoviridae Infections / Q000401:mortality / Q000635:transmission / Q000821:virology*; D012324:RNA-Dependent RNA Polymerase / Q000235:genetics* / Q000378:metabolism; D011995:Recombination, Genetic; D013696:Temperature; D014764:Viral Proteins / Q000235:genetics*; D056189:Viral Tropism; D014774:Virulence / Q000235:genetics; D014779:Virus Replication; D017201:Virus Shedding
chemical_list: D003062:Codon; C057027:PB2 protein, Influenzavirus A; D014764:Viral Proteins; D012324:RNA-Dependent RNA Polymerase