title: Adaptation of an H7N7 equine influenza A virus in mice.
abstract: Wild waterfowl are a reservoir for influenza A viruses, which can be transmitted from these birds to other animal species. Occasionally, influenza A viruses are transmitted to other animal species from animals other than wild waterfowl, e.g. an equine influenza virus has been transmitted to dogs and caused outbreaks. To understand the molecular mechanism by which influenza A viruses adapt to a new animal species, the molecular changes involved in the adaptation of an H7N7 equine influenza A virus were studied in mice. Mutations in the mouse-adapted virus mapped to one amino acid change in the PA protein, one in PB2 and two in PB1. Of these mutations, the Glu-to-Lys substitution at position 627 of PB2 (PB2-E627K) increased virulence appreciably. To understand the mechanism of this increased virulence, a recombinant virus expressing a reporter green fluorescent protein was constructed, thus enabling the effect of this mutation on viral protein expression to be tested in the context of virus replication in situ. It was found that the PB2-E627K substitution in this equine virus contributed to increased viral protein expression and virus replication in mouse cells and enhanced brain invasiveness in mice. These results demonstrate that the importance of the PB2-E627K substitution for mouse adaptation, which was identified previously in human H5N1 isolates, extends to equine influenza A virus.
authors.affiliation: Graduate School of Medicine, Tohoku University, Sendai 980-8575, Japan.|Department of Pathobiological Sciences, University of Wisconsin-Madison, WI 53706, USA.|Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan.
authors.forename: Kyoko
authors.initials: K
authors.lastname: Shinya
authors.affiliation: Department of Pathobiological Sciences, University of Wisconsin-Madison, WI 53706, USA.
authors.forename: Shinji
authors.initials: S
authors.lastname: Watanabe
authors.affiliation: Avian Zoonosis Research Center, Tottori University, Tottori 680-8553, Japan.
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Ito
authors.affiliation: Graduate School of Medicine, Tohoku University, Sendai 980-8575, Japan.
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Kasai
authors.affiliation: Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan.|Department of Pathobiological Sciences, University of Wisconsin-Madison, WI 53706, USA.|International Research Center for Infectious Diseases, Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan.|CREST, Japan Science and Technology Agency, Saitama 332-0012, Japan.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Kawaoka
mesh_terms: D000222:Adaptation, Physiological; D019943:Amino Acid Substitution; D000818:Animals; D001921:Brain / Q000473:pathology / Q000821:virology; D002460:Cell Line; D004285:Dogs; D005260:Female; D006734:Horse Diseases / Q000821:virology; D006736:Horses / Q000821:virology*; D006801:Humans; D053126:Influenza A Virus, H7N7 Subtype / Q000235:genetics / Q000472:pathogenicity* / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D009976:Orthomyxoviridae Infections / Q000473:pathology* / Q000821:virology; D014774:Virulence; D014779:Virus Replication