title: Rapid emergence of a PB2-E627K substitution confers a virulent phenotype to an H9N2 avian influenza virus during adoption in mice.
abstract: The worldwide circulation of H9N2 avian influenza virus in poultry, the greater than 2.3 % positive rate for anti-H9 antibodies in poultry-exposed workers, and several reports of human infection indicate that H9N2 virus is a potential threat to human health. Here, we found three mutations that conferred high virulence to H9N2 virus in mice after four passages. The PB2-E627K substitution rapidly appeared at the second passage and played a decisive role in virulence. Polymerase complexes possessing PB2-E627K displayed 16.1-fold higher viral polymerase activity when compared to the wild-type virus, which may account for enhanced virulence of this virus. The other two substitutions (HA-N313D and HA-N496S) enhanced binding to both α2,3-linked and α2,6-linked sialic acid receptors; however, the HA-N313D and N496S substitutions alone decreased the virulence of mouse-adapted virus. Furthermore, this mouse-adapted virus was still not transmissible among guinea pigs by direct contact (0/3 pairs). Our findings show that adaption in mice enhanced the viral polymerase activity and receptor-binding ability, which resulted in a virulent phenotype in mice but not a transmissible phenotype in guinea pigs, indicating that host factors play an important role in adaptive evolution of influenza in new hosts.
authors.affiliation: Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, 150000, Heilongjiang, China.
authors.forename: Xiaoyu
authors.initials: X
authors.lastname: Sang
authors.forename: Airong
authors.initials: A
authors.lastname: Wang
authors.forename: Tongjie
authors.initials: T
authors.lastname: Chai
authors.forename: Xijun
authors.initials: X
authors.lastname: He
authors.forename: Jie
authors.initials: J
authors.lastname: Ding
authors.forename: Xiaolong
authors.initials: X
authors.lastname: Gao
authors.forename: Yuanguo
authors.initials: Y
authors.lastname: Li
authors.forename: Kun
authors.initials: K
authors.lastname: Zhang
authors.forename: Zhiguang
authors.initials: Z
authors.lastname: Ren
authors.forename: Lin
authors.initials: L
authors.lastname: Li
authors.forename: Zhijun
authors.initials: Z
authors.lastname: Yu
authors.forename: Tiecheng
authors.initials: T
authors.lastname: Wang
authors.forename: Na
authors.initials: N
authors.lastname: Feng
authors.forename: Xuexing
authors.initials: X
authors.lastname: Zheng
authors.forename: Hualei
authors.initials: H
authors.lastname: Wang
authors.forename: Yongkun
authors.initials: Y
authors.lastname: Zhao
authors.forename: Songtao
authors.initials: S
authors.lastname: Yang
authors.forename: Yuwei
authors.initials: Y
authors.lastname: Gao
authors.forename: Xianzhu
authors.initials: X
authors.lastname: Xia
mesh_terms: D000220:Adaptation, Biological; D019943:Amino Acid Substitution; D000818:Animals; D005260:Female; D006168:Guinea Pigs; D053127:Influenza A Virus, H9N2 Subtype / Q000235:genetics / Q000254:growth & development / Q000302:isolation & purification* / Q000502:physiology; D008807:Mice, Inbred BALB C; D020125:Mutation, Missense; D009976:Orthomyxoviridae Infections / Q000635:transmission / Q000821:virology*; D012324:RNA-Dependent RNA Polymerase / Q000235:genetics* / Q000378:metabolism; D012692:Serial Passage; D014764:Viral Proteins / Q000235:genetics* / Q000378:metabolism; D014774:Virulence; D053585:Virus Attachment; D014779:Virus Replication
chemical_list: C057027:PB2 protein, Influenzavirus A; D014764:Viral Proteins; D012324:RNA-Dependent RNA Polymerase