Influenza A variants with reduced susceptibility to baloxavir isolated from Japanese patients are fit and transmit through respiratory droplets

  • Nat Microbiol. 2020 Jan;5(1):27-33. doi: 10.1038/s41564-019-0609-0.
Masaki Imai   #  1 ,  Makoto Yamashita   #  2 ,  Yuko Sakai-Tagawa   #  2 ,  Kiyoko Iwatsuki-Horimoto   #  2 ,  Maki Kiso  2 ,  Jurika Murakami  2 ,  Atsuhiro Yasuhara  2 ,  Kosuke Takada  2 ,  Mutsumi Ito  2 ,  Noriko Nakajima  3 ,  Kenta Takahashi  3 ,  Tiago J S Lopes  2  4 ,  Jayeeta Dutta  5 ,  Zenab Khan  5 ,  Divya Kriti  5 ,  Harm van Bakel  5 ,  Akifumi Tokita  6  7 ,  Haruhisa Hagiwara  7  8 ,  Naomi Izumida  7  9 ,  Haruo Kuroki  10 ,  Tamon Nishino  7  11 ,  Noriyuki Wada  7  12 ,  Michiko Koga  13 ,  Eisuke Adachi  14 ,  Daisuke Jubishi  2  15 ,  Hideki Hasegawa  3  16 ,  Yoshihiro Kawaoka  17  18  19
Affiliations
  • 1. Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, Tokyo, Japan. [email protected].
  • 2. Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, Tokyo, Japan.
  • 3. Department of Pathology, National Institute of Infectious Diseases, Tokyo, Japan.
  • 4. Influenza Research Institute, Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin, Madison, WI, USA.
  • 5. Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
  • 6. Clinic Bambini, Tokyo, Japan.
  • 7. Members of the Tokyo Pediatric Association Public Health Committee, Tokyo, Japan.
  • 8. Hagiwara Clinic, Tokyo, Japan.
  • 9. Akebonocho Clinic, Tokyo, Japan.
  • 10. Sotobo Children's Clinic, Chiba, Japan.
  • 11. Alpaca Kids Ent Clinic, Tokyo, Japan.
  • 12. Wada Pediatric Clinic, Tokyo, Japan.
  • 13. Division of Infectious Diseases, Advanced Clinical Research Center, Institute of Medical Science, University of Tokyo, Tokyo, Japan.
  • 14. Department of Infectious Diseases and Applied Immunology, IMSUT Hospital of the Institute of Medical Science, University of Tokyo, Tokyo, Japan.
  • 15. Nezu Clinic, Tokyo, Japan.
  • 16. Influenza Virus Research Center, National Institute of Infectious Diseases, Tokyo, Japan.
  • 17. Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, Tokyo, Japan. [email protected].
  • 18. Influenza Research Institute, Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin, Madison, WI, USA. [email protected].
  • 19. Department of Special Pathogens, International Research Center for Infectious Diseases, Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo, Japan. [email protected].
  • # Contributed equally.
PMID: 31768027 DOI: 10.1038/s41564-019-0609-0
Abstract

Here we report the isolation of the influenza A/H1N1 2009 pandemic (A/H1N1pdm) and A/H3N2 viruses carrying an I38T mutation in the polymerase acidic protein-a mutation that confers reduced susceptibility to baloxavir marboxil-from patients before and after treatment with baloxavir marboxil in Japan. These variants showed replicative abilities and pathogenicity that is similar to those of wild-type isolates in hamsters; they also transmitted efficiently between ferrets by respiratory droplets.

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