title: A Single Amino Acid in the M1 Protein Responsible for the Different Pathogenic Potentials of H5N1 Highly Pathogenic Avian Influenza Virus Strains.
abstract: Two highly pathogenic avian influenza virus strains, A/duck/Hokkaido/WZ83/2010 (H5N1) (WZ83) and A/duck/Hokkaido/WZ101/2010 (H5N1) (WZ101), which were isolated from wild ducks in Japan, were found to be genetically similar, with only two amino acid differences in their M1 and PB1 proteins at positions 43 and 317, respectively. We found that both WZ83 and WZ101 caused lethal infection in chickens but WZ101 killed them more rapidly than WZ83. Interestingly, ducks experimentally infected with WZ83 showed no or only mild clinical symptoms, whereas WZ101 was highly lethal. We then generated reassortants between these viruses and found that exchange of the M gene segment completely switched the pathogenic phenotype in both chickens and ducks, indicating that the difference in the pathogenicity for these avian species between WZ83 and WZ101 was determined by only a single amino acid in the M1 protein. It was also found that WZ101 showed higher pathogenicity than WZ83 in mice and that WZ83, whose M gene was replaced with that of WZ101, showed higher pathogenicity than wild-type WZ83, although this reassortant virus was not fully pathogenic compared to wild-type WZ101. These results suggest that the amino acid at position 43 of the M1 protein is one of the factors contributing to the pathogenicity of H5N1 highly pathogenic avian influenza viruses in both avian and mammalian hosts.
authors.affiliation: Research Center for Zoonosis Control, Hokkaido University, Sapporo, Japan.
authors.forename: Naganori
authors.initials: N
authors.lastname: Nao
authors.affiliation: Research Center for Zoonosis Control, Hokkaido University, Sapporo, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Kajihara
authors.affiliation: Research Center for Zoonosis Control, Hokkaido University, Sapporo, Japan.
authors.forename: Rashid
authors.initials: R
authors.lastname: Manzoor
authors.affiliation: Research Center for Zoonosis Control, Hokkaido University, Sapporo, Japan.
authors.forename: Junki
authors.initials: J
authors.lastname: Maruyama
authors.affiliation: Research Center for Zoonosis Control, Hokkaido University, Sapporo, Japan.
authors.forename: Reiko
authors.initials: R
authors.lastname: Yoshida
authors.affiliation: Research Center for Zoonosis Control, Hokkaido University, Sapporo, Japan.
authors.forename: Mieko
authors.initials: M
authors.lastname: Muramatsu
authors.affiliation: Research Center for Zoonosis Control, Hokkaido University, Sapporo, Japan.
authors.forename: Hiroko
authors.initials: H
authors.lastname: Miyamoto
authors.affiliation: Research Center for Zoonosis Control, Hokkaido University, Sapporo, Japan.
authors.forename: Manabu
authors.initials: M
authors.lastname: Igarashi
authors.affiliation: Research Center for Zoonosis Control, Hokkaido University, Sapporo, Japan.
authors.forename: Nao
authors.initials: N
authors.lastname: Eguchi
authors.affiliation: Research Center for Zoonosis Control, Hokkaido University, Sapporo, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Sato
authors.affiliation: Research Center for Zoonosis Control, Hokkaido University, Sapporo, Japan.
authors.forename: Tatsunari
authors.initials: T
authors.lastname: Kondoh
authors.affiliation: Graduate School of Veterinary Medicine, Hokkaido University, Sapporo, Japan.
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Okamatsu
authors.affiliation: Graduate School of Veterinary Medicine, Hokkaido University, Sapporo, Japan.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Sakoda
authors.affiliation: Research Center for Zoonosis Control, Hokkaido University, Sapporo, Japan; Global Institution for Collaborative Research and Education, Hokkaido University, Sapporo, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kida
authors.affiliation: Research Center for Zoonosis Control, Hokkaido University, Sapporo, Japan; Global Institution for Collaborative Research and Education, Hokkaido University, Sapporo, Japan; School of Veterinary Medicine, the University of Zambia, Lusaka, Zambia.
authors.forename: Ayato
authors.initials: A
authors.lastname: Takada
mesh_terms: D019943:Amino Acid Substitution; D000818:Animals; D002642:Chick Embryo; D004372:Ducks; D053124:Influenza A Virus, H5N1 Subtype / Q000235:genetics* / Q000472:pathogenicity*; D051379:Mice; D020125:Mutation, Missense; D009976:Orthomyxoviridae Infections / Q000235:genetics*; D014763:Viral Matrix Proteins / Q000235:genetics*
chemical_list: C488936:M1 protein, Influenza A virus; D014763:Viral Matrix Proteins