2. Academic Validation
  3. Influenza A variants with reduced susceptibility to baloxavir isolated from Japanese patients are fit and transmit through respiratory droplets

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

Affiliations

  • 1 Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, Tokyo, Japan. mimai@ims.u-tokyo.ac.jp.
  • 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. yoshihiro.kawaoka@wisc.edu.
  • 18 Influenza Research Institute, Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin, Madison, WI, USA. yoshihiro.kawaoka@wisc.edu.
  • 19 Department of Special Pathogens, International Research Center for Infectious Diseases, Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo, Japan. yoshihiro.kawaoka@wisc.edu.
  • # 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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