Amino acids substitutions in the PB2 protein of H7N9 influenza A viruses are important for virulence in mammalian hosts

Seiya Yamayoshi; Satoshi Fukuyama; Shinya Yamada; Dongming Zhao; Shin Murakami; Ryuta Uraki; Tokiko Watanabe; Yuriko Tomita; Gabriele Neumann; Yoshihiro Kawaoka

doi:10.1038/srep08039

Amino acids substitutions in the PB2 protein of H7N9 influenza A viruses are important for virulence in mammalian hosts

Sci Rep. 2015 Jan 27:5:8039. doi: 10.1038/srep08039.

Authors

Affiliations

¹ Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, Tokyo, Japan.
² 1] Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, Tokyo, Japan [2] ERATO Infection-Induced Host Responses Project, Japan Science and Technology Agency, Saitama, Japan.
³ Department of Special Pathogens, International Research Center for Infectious Diseases, Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo, Japan.
⁴ Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, 575 Science Drive, Madison, WI, USA.
⁵ 1] Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, Tokyo, Japan [2] ERATO Infection-Induced Host Responses Project, Japan Science and Technology Agency, Saitama, Japan [3] Department of Special Pathogens, International Research Center for Infectious Diseases, Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo, Japan [4] Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, 575 Science Drive, Madison, WI, USA.

Abstract

We tested the biological significance of two amino acid mutations in the PB2 protein (glutamic acid to lysine at position 627 and aspartic acid to asparagine at position 701) of A(H7N9) viruses for mammalian adaptation. Mutants were assessed for their viral polymerase activities, growth kinetics in mammalian and avian cells, and pathogenicity in mice. We found that lysine at position 627 and asparagine at position 701 in PB2 are essential for mammalian adaptation of A(H7N9) viruses.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Amino Acid Substitution
Animals
Body Weight
Cell Line
Dogs
Female
Genes, Reporter
Humans
Influenza A Virus, H7N9 Subtype / metabolism*
Influenza A Virus, H7N9 Subtype / pathogenicity
Lung / virology
Madin Darby Canine Kidney Cells
Mice
Mice, Inbred BALB C
Nasal Cavity / virology
Viral Proteins / genetics*
Virulence / genetics*
Virus Replication

Substances

PB2 protein, influenza virus
Viral Proteins

Abstract

Publication types

MeSH terms

Substances

Grants and funding