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Published ahead of print 26 December 2013, doi: 10.1128/JVI.03155-13 JVI.03155-13
Virulence-Affecting Amino Acid Changes in the PA Protein of H7N9 Influenza A Viruses
Seiya Yamayoshi1,
Shinya Yamada1,
Satoshi Fukuyama2,
Shin Murakami3,
Dongming Zhao2,
Ryuta Uraki1,
Tokiko Watanabe2,
Yuriko Tomita2,
Catherine Macken4,
Gabriele Neumann5 and
Yoshihiro Kawaoka1,2,3,5#
+ Author Affiliations
1Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, Tokyo, Japan
2ERATO Infection-Induced Host Responses Project, Japan Science and Technology Agency, Saitama, Japan
3Department of Special Pathogens, International Research Center for Infectious Diseases, Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo, Japan
4Theoretical Division, Los Alamos National Laboratory, Los Alamos, New Mexico, USA
5Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, 575 Science Drive, Madison, WI, USA
ABSTRACT
Novel avian-origin influenza A(H7N9) viruses were first reported to infect humans in March 2013. To date, 143 human cases, including 45 deaths, have been recorded. By using sequence comparisons and phylogenetic and ancestral inference analyses, we identified several distinct amino acids in the A(H7N9) polymerase PA protein, some of which may be mammalian-adapting. Mutant viruses possessing some of these amino acid changes, singly or in combination, were assessed for their polymerase activities and growth kinetics in mammalian and avian cells, and for their virulence in mice. We identified several mutants that were slightly more virulent in mice than the wild-type A(H7N9) virus, A/Anhui/1/2013. These mutants also exhibited increased polymerase activity in human cells, but not in avian cells. Our findings indicate that the PA protein of A(H7N9) viruses has several amino acid substitutions that are attenuating in mammals.
Virulence-Affecting Amino Acid Changes in the PA Protein of H7N9 Influenza A Viruses
Seiya Yamayoshi1,
Shinya Yamada1,
Satoshi Fukuyama2,
Shin Murakami3,
Dongming Zhao2,
Ryuta Uraki1,
Tokiko Watanabe2,
Yuriko Tomita2,
Catherine Macken4,
Gabriele Neumann5 and
Yoshihiro Kawaoka1,2,3,5#
+ Author Affiliations
1Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, Tokyo, Japan
2ERATO Infection-Induced Host Responses Project, Japan Science and Technology Agency, Saitama, Japan
3Department of Special Pathogens, International Research Center for Infectious Diseases, Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo, Japan
4Theoretical Division, Los Alamos National Laboratory, Los Alamos, New Mexico, USA
5Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, 575 Science Drive, Madison, WI, USA
ABSTRACT
Novel avian-origin influenza A(H7N9) viruses were first reported to infect humans in March 2013. To date, 143 human cases, including 45 deaths, have been recorded. By using sequence comparisons and phylogenetic and ancestral inference analyses, we identified several distinct amino acids in the A(H7N9) polymerase PA protein, some of which may be mammalian-adapting. Mutant viruses possessing some of these amino acid changes, singly or in combination, were assessed for their polymerase activities and growth kinetics in mammalian and avian cells, and for their virulence in mice. We identified several mutants that were slightly more virulent in mice than the wild-type A(H7N9) virus, A/Anhui/1/2013. These mutants also exhibited increased polymerase activity in human cells, but not in avian cells. Our findings indicate that the PA protein of A(H7N9) viruses has several amino acid substitutions that are attenuating in mammals.
