title: Growth of H5N1 influenza A viruses in the upper respiratory tracts of mice.
abstract: Highly pathogenic avian H5N1 influenza A viruses have spread throughout Asia, Europe, and Africa, raising serious worldwide concern about their pandemic potential. Although more than 250 people have been infected with these viruses, with a consequent high rate of mortality, the molecular mechanisms responsible for the efficient transmission of H5N1 viruses among humans remain elusive. We used a mouse model to examine the role of the amino acid at position 627 of the PB2 viral protein in efficient replication of H5N1 viruses in the mammalian respiratory tract. Viruses possessing Lys at position 627 of PB2 replicated efficiently in lungs and nasal turbinates, as well as in cells, even at the lower temperature of 33 degrees C. Those viruses possessing Glu at this position replicated less well in nasal turbinates than in lungs, and less well in cells at the lower temperature. These results suggest that Lys at PB2-627 confers to avian H5N1 viruses the advantage of efficient growth in the upper and lower respiratory tracts of mammals. Therefore, efficient viral growth in the upper respiratory tract may provide a platform for the adaptation of avian H5N1 influenza viruses to humans and for efficient person-to-person virus transmission, in the context of changes in other viral properties including specificity for human (sialic acid alpha-2,6-galactose containing) receptors.
authors.affiliation: Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, Wisconsin, USA.
authors.forename: Masato
authors.initials: M
authors.lastname: Hatta
authors.forename: Yasuko
authors.initials: Y
authors.lastname: Hatta
authors.forename: Jin Hyun
authors.initials: JH
authors.lastname: Kim
authors.forename: Shinji
authors.initials: S
authors.lastname: Watanabe
authors.forename: Kyoko
authors.initials: K
authors.lastname: Shinya
authors.forename: Tung
authors.initials: T
authors.lastname: Nguyen
authors.forename: Phuong Song
authors.initials: PS
authors.lastname: Lien
authors.forename: Quynh Mai
authors.initials: QM
authors.lastname: Le
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Kawaoka
mesh_terms: D000818:Animals; D002460:Cell Line; D006801:Humans; D053124:Influenza A Virus, H5N1 Subtype / Q000472:pathogenicity* / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D009154:Mutation; D009976:Orthomyxoviridae Infections / Q000235:genetics / Q000821:virology*; D016133:Polymerase Chain Reaction; D012324:RNA-Dependent RNA Polymerase / Q000235:genetics*; D012141:Respiratory Tract Infections / Q000235:genetics / Q000821:virology*; D014764:Viral Proteins / Q000737:chemistry / Q000235:genetics*; D014779:Virus Replication
chemical_list: C057027:PB2 protein, Influenzavirus A; D014764:Viral Proteins; D012324:RNA-Dependent RNA Polymerase