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Pathogenesis and Immunity

Genetic Compatibility of Reassortants between Avian H5N1 and H9N2 Influenza Viruses with Higher Pathogenicity in Mammals

Yasuha Arai, Madiha S. Ibrahim, Emad M. Elgendy, Tomo Daidoji, Takao Ono, Yasuo Suzuki, Takaaki Nakaya, Kazuhiko Matsumoto, Yohei Watanabe
Stacey Schultz-Cherry, Editor
Yasuha Arai
Department of Infectious Diseases, Kyoto Prefectural University of Medicine, Kyoto, JapanCREST, Japan Science and Technology Agency, Saitama, Japan
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Madiha S. Ibrahim
Department of Microbiology and Immunology, Faculty of Veterinary Medicine, Damanhour University, Damanhour, Egypt
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Emad M. Elgendy
Department of Microbiology and Immunology, Faculty of Veterinary Medicine, Damanhour University, Damanhour, Egypt
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Tomo Daidoji
Department of Infectious Diseases, Kyoto Prefectural University of Medicine, Kyoto, Japan
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Takao Ono
The Institute of Scientific and Industrial Research, Osaka University, Osaka, JapanCREST, Japan Science and Technology Agency, Saitama, Japan
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Yasuo Suzuki
College of Life and Health Sciences, Chubu University, Aichi, JapanCREST, Japan Science and Technology Agency, Saitama, Japan
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Takaaki Nakaya
Department of Infectious Diseases, Kyoto Prefectural University of Medicine, Kyoto, Japan
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Kazuhiko Matsumoto
The Institute of Scientific and Industrial Research, Osaka University, Osaka, JapanCREST, Japan Science and Technology Agency, Saitama, Japan
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Yohei Watanabe
Department of Infectious Diseases, Kyoto Prefectural University of Medicine, Kyoto, JapanCREST, Japan Science and Technology Agency, Saitama, Japan
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Stacey Schultz-Cherry
St. Jude Children’s Research Hospital
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DOI: 10.1128/JVI.01969-18
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ABSTRACT

The cocirculation of H5N1 and H9N2 avian influenza viruses in birds in Egypt provides reassortment opportunities between these two viruses. However, little is known about the emergence potential of reassortants derived from Egyptian H5N1 and H9N2 viruses and about the biological properties of such reassortants. To evaluate the potential public health risk of reassortants of these viruses, we used reverse genetics to generate the 63 possible reassortants derived from contemporary Egyptian H5N1 and H9N2 viruses, containing the H5N1 surface gene segments and combinations of the H5N1 and H9N2 internal gene segments, and analyzed their genetic compatibility, replication ability, and virulence in mice. Genes in the reassortants showed remarkably high compatibility. The replication of most reassortants was higher than the parental H5N1 virus in human cells. Six reassortants were thought to emerge in birds under neutral or positive selective pressure, and four of them had higher pathogenicity in vivo than the parental H5N1 and H9N2 viruses. Our results indicated that H5N1-H9N2 reassortants could be transmitted efficiently to mammals with significant public health risk if they emerge in Egypt, although the viruses might not emerge frequently in birds.

IMPORTANCE Close interaction between avian influenza (AI) viruses and humans in Egypt appears to have resulted in many of the worldwide cases of human infections by both H5N1 and H9N2 AI viruses. Egypt is regarded as a hot spot of AI virus evolution. Although no natural reassortant of H5N1 and H9N2 AI viruses has been reported so far, their cocirculation in Egypt may allow emergence of reassortants that may present a significant public health risk. Using reverse genetics, we report here the first comprehensive data showing that H5N1-N9N2 reassortants have fairly high genetic compatibility and possibly higher pathogenicity in mammals, including humans, than the parental viruses. Our results provide insight into the emergence potential of avian H5N1-H9N2 reassortants that may pose a high public health risk.

FOOTNOTES

    • Received 5 November 2018.
    • Accepted 6 November 2018.
    • Accepted manuscript posted online 21 November 2018.
  • Supplemental material for this article may be found at https://doi.org/10.1128/JVI.01969-18.

  • Copyright © 2019 Arai et al.

This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license.

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Genetic Compatibility of Reassortants between Avian H5N1 and H9N2 Influenza Viruses with Higher Pathogenicity in Mammals
Yasuha Arai, Madiha S. Ibrahim, Emad M. Elgendy, Tomo Daidoji, Takao Ono, Yasuo Suzuki, Takaaki Nakaya, Kazuhiko Matsumoto, Yohei Watanabe
Journal of Virology Feb 2019, 93 (4) e01969-18; DOI: 10.1128/JVI.01969-18

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Genetic Compatibility of Reassortants between Avian H5N1 and H9N2 Influenza Viruses with Higher Pathogenicity in Mammals
Yasuha Arai, Madiha S. Ibrahim, Emad M. Elgendy, Tomo Daidoji, Takao Ono, Yasuo Suzuki, Takaaki Nakaya, Kazuhiko Matsumoto, Yohei Watanabe
Journal of Virology Feb 2019, 93 (4) e01969-18; DOI: 10.1128/JVI.01969-18
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KEYWORDS

H5N1
H9N2
influenza reassortants
pathogenicity
public health risk

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