Identification of mammalian-adapting mutations in the polymerase complex of an avian H5N1 influenza virus

Andrew S. Taft, Makoto Ozawa, Adam Fitch, Jay V. Depasse, Peter J. Halfmann, Lindsay Hill-Batorski, Masato Hatta, Thomas C. Friedrich, Tiago J S Lopes, Eileen A. Maher, Elodie Ghedin, Catherine A. Macken, Gabriele Neumann, Yoshihiro Kawaoka

Research output: Contribution to journalArticle

Abstract

Avian influenza viruses of the H5N1 subtype pose a serious global health threat due to the high mortality (>60%) associated with the disease caused by these viruses and the lack of protective antibodies to these viruses in the general population. The factors that enable avian H5N1 influenza viruses to replicate in humans are not completely understood. Here we use a high-throughput screening approach to identify novel mutations in the polymerase genes of an avian H5N1 virus that confer efficient polymerase activity in mammalian cells. Several of the identified mutations (which have previously been found in natural isolates) increase viral replication in mammalian cells and virulence in infected mice compared with the wild-type virus. The identification of amino-acid mutations in avian H5N1 influenza virus polymerase complexes that confer increased replication and virulence in mammals is important for the identification of circulating H5N1 viruses with an increased potential to infect humans.

Original languageEnglish (US)
Article number7491
JournalNature Communications
Volume6
DOIs
StatePublished - Jun 17 2015

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H5N1 Subtype Influenza A Virus
influenza
Influenza in Birds
viruses
mutations
Orthomyxoviridae
Viruses
Mutation
Virulence
virulence
Population Growth
Virus Diseases
Mammals
Cells
Amino Acids
mammals
Mortality
Antibodies
mortality
antibodies

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Chemistry(all)
  • Physics and Astronomy(all)

Cite this

Taft, A. S., Ozawa, M., Fitch, A., Depasse, J. V., Halfmann, P. J., Hill-Batorski, L., ... Kawaoka, Y. (2015). Identification of mammalian-adapting mutations in the polymerase complex of an avian H5N1 influenza virus. Nature Communications, 6, [7491]. https://doi.org/10.1038/ncomms8491

Identification of mammalian-adapting mutations in the polymerase complex of an avian H5N1 influenza virus. / Taft, Andrew S.; Ozawa, Makoto; Fitch, Adam; Depasse, Jay V.; Halfmann, Peter J.; Hill-Batorski, Lindsay; Hatta, Masato; Friedrich, Thomas C.; Lopes, Tiago J S; Maher, Eileen A.; Ghedin, Elodie; Macken, Catherine A.; Neumann, Gabriele; Kawaoka, Yoshihiro.

In: Nature Communications, Vol. 6, 7491, 17.06.2015.

Research output: Contribution to journalArticle

Taft, AS, Ozawa, M, Fitch, A, Depasse, JV, Halfmann, PJ, Hill-Batorski, L, Hatta, M, Friedrich, TC, Lopes, TJS, Maher, EA, Ghedin, E, Macken, CA, Neumann, G & Kawaoka, Y 2015, 'Identification of mammalian-adapting mutations in the polymerase complex of an avian H5N1 influenza virus', Nature Communications, vol. 6, 7491. https://doi.org/10.1038/ncomms8491
Taft, Andrew S. ; Ozawa, Makoto ; Fitch, Adam ; Depasse, Jay V. ; Halfmann, Peter J. ; Hill-Batorski, Lindsay ; Hatta, Masato ; Friedrich, Thomas C. ; Lopes, Tiago J S ; Maher, Eileen A. ; Ghedin, Elodie ; Macken, Catherine A. ; Neumann, Gabriele ; Kawaoka, Yoshihiro. / Identification of mammalian-adapting mutations in the polymerase complex of an avian H5N1 influenza virus. In: Nature Communications. 2015 ; Vol. 6.
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