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 and Yoshihiro Kawaoka ()
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Andrew S. Taft: Influenza Research Institute, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, Wisconsin 53711, USA
Makoto Ozawa: Laboratory of Animal Hygiene, Joint Faculty of Veterinary Medicine, Kagoshima University
Adam Fitch: University of Pittsburgh School of Medicine
Jay V. Depasse: University of Pittsburgh School of Medicine
Peter J. Halfmann: Influenza Research Institute, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, Wisconsin 53711, USA
Lindsay Hill-Batorski: Influenza Research Institute, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, Wisconsin 53711, USA
Masato Hatta: Influenza Research Institute, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, Wisconsin 53711, USA
Thomas C. Friedrich: Wisconsin National Primate Research Center
Tiago J. S. Lopes: Influenza Research Institute, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, Wisconsin 53711, USA
Eileen A. Maher: Influenza Research Institute, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, Wisconsin 53711, USA
Elodie Ghedin: University of Pittsburgh School of Medicine
Catherine A. Macken: Bioinformatics Institute, University of Auckland
Gabriele Neumann: Influenza Research Institute, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, Wisconsin 53711, USA
Yoshihiro Kawaoka: Influenza Research Institute, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, Wisconsin 53711, USA

Nature Communications, 2015, vol. 6, issue 1, 1-12

Abstract: 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.

Date: 2015
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DOI: 10.1038/ncomms8491

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