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

doi:10.1038/s41564-019-0609-0

. 2020 Jan;5(1):27-33.

doi: 10.1038/s41564-019-0609-0. Epub 2019 Nov 25.

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

Masaki Imai^#¹, Makoto Yamashita^#², Yuko Sakai-Tagawa^#², Kiyoko Iwatsuki-Horimoto^#², Maki Kiso², Jurika Murakami², Atsuhiro Yasuhara², Kosuke Takada², Mutsumi Ito², Noriko Nakajima³, Kenta Takahashi³, Tiago J S Lopes^{2

4}, Jayeeta Dutta⁵, Zenab Khan⁵, Divya Kriti⁵, Harm van Bakel⁵, Akifumi Tokita^{6

7}, Haruhisa Hagiwara^{7

8}, Naomi Izumida^{7

9}, Haruo Kuroki¹⁰, Tamon Nishino^{7

11}, Noriyuki Wada^{7

12}, Michiko Koga¹³, Eisuke Adachi¹⁴, 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. 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

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

Masaki Imai et al. Nat Microbiol. 2020 Jan.

. 2020 Jan;5(1):27-33.

doi: 10.1038/s41564-019-0609-0. Epub 2019 Nov 25.

Authors

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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Comment in

Emerging antiviral resistance.
Kormuth KA, Lakdawala SS. Kormuth KA, et al. Nat Microbiol. 2020 Jan;5(1):4-5. doi: 10.1038/s41564-019-0639-7. Nat Microbiol. 2020. PMID: 31857727 No abstract available.

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References

1. Noshi, T. et al. In vitro characterization of baloxavir acid, a first-in-class cap-dependent endonuclease inhibitor of the influenza virus polymerase PA subunit. Antiviral Res. 160, 109–117 (2018). - DOI
1. Omoto, S. et al. Characterization of influenza virus variants induced by treatment with the endonuclease inhibitor baloxavir marboxil. Sci. Rep. 8, 9633 (2018). - DOI
1. Hayden, F. G. et al. Baloxavir marboxil for uncomplicated influenza in adults and adolescents. N. Engl. J. Med. 379, 913–923 (2018). - DOI
1. Takashita, E. et al. Detection of influenza A(H3N2) viruses exhibiting reduced susceptibility to the novel cap-dependent endonuclease inhibitor baloxavir in Japan, December 2018. Euro Surveill. 24, 1800698 (2019). - PMC
1. Takashita, E. et al. Influenza A(H3N2) virus exhibiting reduced susceptibility to baloxavir due to a polymerase acidic subunit I38T substitution detected from a hospitalised child without prior baloxavir treatment, Japan, January 2019. Euro Surveill. 24, 1900170 (2019). - PMC

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[1] Noshi, T. et al. In vitro characterization of baloxavir acid, a first-in-class cap-dependent endonuclease inhibitor of the influenza virus polymerase PA subunit. Antiviral Res. 160, 109–117 (2018). - DOI

[2] Noshi, T. et al. In vitro characterization of baloxavir acid, a first-in-class cap-dependent endonuclease inhibitor of the influenza virus polymerase PA subunit. Antiviral Res. 160, 109–117 (2018). - DOI

[3] Omoto, S. et al. Characterization of influenza virus variants induced by treatment with the endonuclease inhibitor baloxavir marboxil. Sci. Rep. 8, 9633 (2018). - DOI

[4] Omoto, S. et al. Characterization of influenza virus variants induced by treatment with the endonuclease inhibitor baloxavir marboxil. Sci. Rep. 8, 9633 (2018). - DOI

[5] Hayden, F. G. et al. Baloxavir marboxil for uncomplicated influenza in adults and adolescents. N. Engl. J. Med. 379, 913–923 (2018). - DOI

[6] Hayden, F. G. et al. Baloxavir marboxil for uncomplicated influenza in adults and adolescents. N. Engl. J. Med. 379, 913–923 (2018). - DOI

[7] Takashita, E. et al. Detection of influenza A(H3N2) viruses exhibiting reduced susceptibility to the novel cap-dependent endonuclease inhibitor baloxavir in Japan, December 2018. Euro Surveill. 24, 1800698 (2019). - PMC

[8] Takashita, E. et al. Detection of influenza A(H3N2) viruses exhibiting reduced susceptibility to the novel cap-dependent endonuclease inhibitor baloxavir in Japan, December 2018. Euro Surveill. 24, 1800698 (2019). - PMC

[9] Takashita, E. et al. Influenza A(H3N2) virus exhibiting reduced susceptibility to baloxavir due to a polymerase acidic subunit I38T substitution detected from a hospitalised child without prior baloxavir treatment, Japan, January 2019. Euro Surveill. 24, 1900170 (2019). - PMC

[10] Takashita, E. et al. Influenza A(H3N2) virus exhibiting reduced susceptibility to baloxavir due to a polymerase acidic subunit I38T substitution detected from a hospitalised child without prior baloxavir treatment, Japan, January 2019. Euro Surveill. 24, 1900170 (2019). - PMC

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

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

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