title: Biological and structural characterization of a host-adapting amino acid in influenza virus.
abstract: Two amino acids (lysine at position 627 or asparagine at position 701) in the polymerase subunit PB2 protein are considered critical for the adaptation of avian influenza A viruses to mammals. However, the recently emerged pandemic H1N1 viruses lack these amino acids. Here, we report that a basic amino acid at position 591 of PB2 can compensate for the lack of lysine at position 627 and confers efficient viral replication to pandemic H1N1 viruses in mammals. Moreover, a basic amino acid at position 591 of PB2 substantially increased the lethality of an avian H5N1 virus in mice. We also present the X-ray crystallographic structure of the C-terminus of a pandemic H1N1 virus PB2 protein. Arginine at position 591 fills the cleft found in H5N1 PB2 proteins in this area, resulting in differences in surface shape and charge for H1N1 PB2 proteins. These differences may affect the protein's interaction with viral and/or cellular factors, and hence its ability to support virus replication in mammals.
authors.affiliation: Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, Tokyo, Japan.
authors.forename: Shinya
authors.initials: S
authors.lastname: Yamada
authors.forename: Masato
authors.initials: M
authors.lastname: Hatta
authors.forename: Bart L
authors.initials: BL
authors.lastname: Staker
authors.forename: Shinji
authors.initials: S
authors.lastname: Watanabe
authors.forename: Masaki
authors.initials: M
authors.lastname: Imai
authors.forename: Kyoko
authors.initials: K
authors.lastname: Shinya
authors.forename: Yuko
authors.initials: Y
authors.lastname: Sakai-Tagawa
authors.forename: Mutsumi
authors.initials: M
authors.lastname: Ito
authors.forename: Makoto
authors.initials: M
authors.lastname: Ozawa
authors.forename: Tokiko
authors.initials: T
authors.lastname: Watanabe
authors.forename: Saori
authors.initials: S
authors.lastname: Sakabe
authors.forename: Chengjun
authors.initials: C
authors.lastname: Li
authors.forename: Jin Hyun
authors.initials: JH
authors.lastname: Kim
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Myler
authors.forename: Isabelle
authors.initials: I
authors.lastname: Phan
authors.forename: Amy
authors.initials: A
authors.lastname: Raymond
authors.forename: Eric
authors.initials: E
authors.lastname: Smith
authors.forename: Robin
authors.initials: R
authors.lastname: Stacy
authors.forename: Chairul A
authors.initials: CA
authors.lastname: Nidom
authors.forename: Simon M
authors.initials: SM
authors.lastname: Lank
authors.forename: Roger W
authors.initials: RW
authors.lastname: Wiseman
authors.forename: Benjamin N
authors.initials: BN
authors.lastname: Bimber
authors.forename: David H
authors.initials: DH
authors.lastname: O'Connor
authors.forename: Gabriele
authors.initials: G
authors.lastname: Neumann
authors.forename: Lance J
authors.initials: LJ
authors.lastname: Stewart
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Kawaoka
mesh_terms: D000596:Amino Acids / Q000737:chemistry*; D000818:Animals; D018360:Crystallography, X-Ray; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000235:genetics / Q000472:pathogenicity* / Q000502:physiology; D020836:Protein Structure, Quaternary; D014764:Viral Proteins / Q000737:chemistry* / Q000235:genetics; D014774:Virulence / Q000235:genetics; D014779:Virus Replication
chemical_list: D000596:Amino Acids; C502893:PB2 protein, influenza virus; D014764:Viral Proteins