Influenza A(H1N1)pdm09 virus exhibiting reduced susceptibility to baloxavir due to a PA E23K substitution detected from a child without baloxavir treatment

Emi Takashita; Takashi Abe; Hiroko Morita; Shiho Nagata; Seiichiro Fujisaki; Hideka Miura; Masayuki Shirakura; Noriko Kishida; Kazuya Nakamura; Tomoko Kuwahara; Keiko Mitamura; Masataka Ichikawa; Masahiko Yamazaki; Shinji Watanabe; Hideki Hasegawa; Influenza Virus Surveillance Group of Japan

doi:10.1016/j.antiviral.2020.104828

Influenza A(H1N1)pdm09 virus exhibiting reduced susceptibility to baloxavir due to a PA E23K substitution detected from a child without baloxavir treatment

Antiviral Res. 2020 Aug:180:104828. doi: 10.1016/j.antiviral.2020.104828. Epub 2020 Jun 20.

Authors

Emi Takashita¹, Takashi Abe², Hiroko Morita³, Shiho Nagata³, Seiichiro Fujisaki³, Hideka Miura³, Masayuki Shirakura³, Noriko Kishida³, Kazuya Nakamura³, Tomoko Kuwahara³, Keiko Mitamura⁴, Masataka Ichikawa⁵, Masahiko Yamazaki⁶, Shinji Watanabe³, Hideki Hasegawa³; Influenza Virus Surveillance Group of Japan

Collaborators

Influenza Virus Surveillance Group of Japan:
Rika Komagome⁷, Asami Ohnishi⁸, Rika Tsutsui⁹, Masaki Takahashi¹⁰, Mie Sasaki¹¹, Shiho Tamura¹², Chihiro Shibata¹³, Kenichi Komabayashi¹⁴, Nozomi Saito¹⁵, Aoi Saito¹⁶, Fuminori Mizukoshi¹⁷, Akira Wakatsuki¹⁸, Hiroyuki Tsukagoshi¹⁹, Noriko Suzuki²⁰, Yuka Uno²¹, Noriko Oitate²², Wakako Nishikawa²³, Mami Nagashima²⁴, Sumi Watanabe²⁵, Chiharu Kawakami²⁶, Hideaki Shimizu²⁷, Hazime Amano²⁸, Satoko Kanazawa²⁹, Kaori Watanabe³⁰, Kazunari Yamamoto³¹, Tetsuya Yoneda³², Sachiko Nakamura³³, Kaori Sato³⁴, Masayuki Oonuma³⁵, Michiko Takeuchi³⁶, Erina Tanaka³⁷, Masahiro Nishioka³⁸, Yusuke Sato³⁹, Yukiko Sakai⁴⁰, Takaharu Maehata⁴¹, Toshihiko Furuta⁴², Yoshihiro Yasui⁴³, Takuya Yano⁴⁴, Asa Tanino⁴⁵, Sachi Hirata⁴⁶, Akiko Nagasao⁴⁷, Satoshi Hiroi⁴⁸, Hideyuki Kubo⁴⁸, Fumika Okayama⁴⁹, Tomohiro Oshibe⁵⁰, Ai Mori⁵¹, Ryutaro Murayama⁵², Shoko Chiba⁵³, Yuki Matsui⁵⁴, Yuko Kiguchi⁵⁵, Koji Takeuchi⁵⁶, Tetsuo Mita⁵⁷, Kayoko Nomiya⁵⁸, Yukie Shimazu⁵⁹, Yoshiki Fujii⁶⁰, Shoichi Toda⁶¹, Yumiko Kawakami⁶², Yukari Terajima⁶³, Mayumi Yamashita⁶⁴, Tomiyo Takahashi⁶⁵, Yuki Ashizuka⁶⁶, Chinami Wasano⁶⁷, Takashi Kimura⁶⁸, Sanae Moroishi⁶⁹, Miho Urakawa⁷⁰, Takashi Sakai⁷¹, Kaori Nishizawa⁷², Toru Hayashi⁷³, Yu Matsuura⁷⁴, Yuka Hamada⁷⁵, Yumani Kuba⁷⁶

Affiliations

¹ Influenza Virus Research Center, National Institute of Infectious Diseases, Gakuen 4-7-1, Musashimurayama, Tokyo, 208-0011, Japan. Electronic address: emitaka@nih.go.jp.
² Abe Children's Clinic, Minowa 2-15-22, Kohoku, Yokohama, Kanagawa, 223-0051, Japan.
³ Influenza Virus Research Center, National Institute of Infectious Diseases, Gakuen 4-7-1, Musashimurayama, Tokyo, 208-0011, Japan.
⁴ Eiju General Hospital, Higashi Ueno 2-23-16, Taito, Tokyo, 110-8645, Japan.
⁵ Ichikawa Children's Clinic, Higashi Odake 1544-3, Isehara, Kanagawa, 259-1133, Japan.
⁶ Zama Children's Clinic, Tatsuno Dai 2-20-24, Zama, Kanagawa, 252-0023, Japan.
⁷ Hokkaido Institute of Public Health, Japan.
⁸ Sapporo City Institute of Public Health, Japan.
⁹ Aomori Prefectural Public Health and Environment Center, Japan.
¹⁰ Iwate Prefectural Research Institute for Environmental Sciences and Public Health, Japan.
¹¹ Miyagi Prefectural Institute of Public Health and Environment, Japan.
¹² Sendai City Institute of Public Health, Japan.
¹³ Akita Prefectural Research Center for Public Health and Environment, Japan.
¹⁴ Yamagata Prefectural Institute of Public Health, Japan.
¹⁵ Fukushima Prefectural Institute of Public Health, Japan.
¹⁶ Ibaraki Prefectural Institute of Public Health, Japan.
¹⁷ Tochigi Prefectural Institute of Public Health and Environmental Sciences, Japan.
¹⁸ Utsunomiya City Institute of Public Health and Environment Science, Japan.
¹⁹ Gunma Prefectural Institute of Public Health and Environmental Sciences, Japan.
²⁰ Saitama Institute of Public Health, Japan.
²¹ Saitama City Institute of Health Science and Research, Japan.
²² Chiba Prefectural Institute of Public Health, Japan.
²³ Chiba City Institute of Health and Environment, Japan.
²⁴ Tokyo Metropolitan Institute of Public Health, Japan.
²⁵ Kanagawa Prefectural Institute of Public Health, Japan.
²⁶ Yokohama City Institute of Public Health, Japan.
²⁷ Kawasaki City Institute of Public Health, Japan.
²⁸ Yokosuka Institute of Public Health, Japan.
²⁹ Sagamihara City Institute of Public Health, Japan.
³⁰ Niigata Prefectural Institute of Public Health and Environmental Sciences, Japan.
³¹ Niigata City Institute of Public Health and Environment, Japan.
³² Toyama Institute of Health, Japan.
³³ Ishikawa Prefectural Institute of Public Health and Environmental Science, Japan.
³⁴ Fukui Prefectural Institute of Public Health and Environmental Science, Japan.
³⁵ Yamanashi Institute for Public Health, Japan.
³⁶ Nagano Environmental Conservation Research Institute, Japan.
³⁷ Nagano City Health Center, Japan.
³⁸ Gifu Prefectural Research Institute for Health and Environmental Sciences, Japan.
³⁹ Gifu Municipal Institute of Public Health, Japan.
⁴⁰ Shizuoka Institute of Environment and Hygiene, Japan.
⁴¹ Shizuoka City Institute of Environmental Sciences and Public Health, Japan.
⁴² Hamamatsu City Health Environment Research Center, Japan.
⁴³ Aichi Prefectural Institute of Public Health, Japan.
⁴⁴ Mie Prefecture Health and Environment Research Institute, Japan.
⁴⁵ Shiga Prefectural Institute of Public Health, Japan.
⁴⁶ Kyoto Prefectural Institute of Public Health and Environment, Japan.
⁴⁷ Kyoto City Institute of Health and Environmental Sciences, Japan.
⁴⁸ Osaka Institute of Public Health, Japan.
⁴⁹ Sakai City Institute of Public Health, Japan.
⁵⁰ Hyogo Prefectural Institute of Public Health Science, Japan.
⁵¹ Kobe Institute of Health, Japan.
⁵² Amagasaki City Institute of Public Health, Japan.
⁵³ Nara Prefecture Institute of Health, Japan.
⁵⁴ Wakayama Prefectural Research Center of Environment and Public Health, Japan.
⁵⁵ Wakayama City Institute of Public Health, Japan.
⁵⁶ Tottori Prefectural Institute of Public Health and Environmental Science, Japan.
⁵⁷ Shimane Prefectural Institute of Public Health and Environmental Science, Japan.
⁵⁸ Okayama Prefectural Institute for Environmental Science and Public Health, Japan.
⁵⁹ Hiroshima Prefectural Technology Research Institute, Japan.
⁶⁰ Hiroshima City Institute of Public Health, Japan.
⁶¹ Yamaguchi Prefectural Institute of Public Health and Environment, Japan.
⁶² Tokushima Prefectural Public Health, Pharmaceutical and Environmental Sciences Center, Japan.
⁶³ Kagawa Prefectural Research Institute for Environmental Sciences and Public Health, Japan.
⁶⁴ Ehime Prefecture Institute of Public Health and Environmental Science, Japan.
⁶⁵ Kochi Public Health and Environmental Science Research Institute, Japan.
⁶⁶ Fukuoka Institute of Health and Environmental Sciences, Japan.
⁶⁷ Fukuoka City Institute of Health and Environment, Japan.
⁶⁸ Kitakyushu City Institute of Health and Environmental Sciences, Japan.
⁶⁹ Saga Prefectural Institute of Public Health and Pharmaceutical Research, Japan.
⁷⁰ Nagasaki Prefectural Institute for Environment Research and Public Health, Japan.
⁷¹ Kumamoto Prefectural Institute of Public-Health and Environmental Science, Japan.
⁷² Kumamoto City Environmental Research Center, Japan.
⁷³ Oita Prefectural Institute of Health and Environment, Japan.
⁷⁴ Miyazaki Prefectural Institute for Public Health and Environment, Japan.
⁷⁵ Kagoshima Prefectural Institute for Environmental Research and Public Health, Japan.
⁷⁶ Okinawa Prefectural Institute of Health and Environment, Japan.

PMID: 32574689
DOI: 10.1016/j.antiviral.2020.104828

Abstract

Human-to-human transmission of PA I38 mutant influenza A(H3N2) viruses with reduced baloxavir susceptibility has been reported in Japan. In December 2019, we detected a PA E23K mutant A(H1N1)pdm09 virus from a child without baloxavir treatment. The PA E23K mutant virus exhibited reduced baloxavir susceptibility but remained susceptible to neuraminidase inhibitors. Epidemiological data suggest possible transmission of this PA E23K mutant virus among humans, although its growth capability relative to that of the wild-type virus was reduced. Therefore, baloxavir susceptibility monitoring of influenza viruses is essential.

Keywords: Baloxavir; Cap-dependent endonuclease inhibitor; Influenza; Resistance.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Amino Acid Substitution
Animals
Antiviral Agents / pharmacology*
Child
Dibenzothiepins / pharmacology*
Dogs
Drug Resistance, Viral / genetics*
Humans
Influenza A Virus, H1N1 Subtype / drug effects*
Influenza A Virus, H1N1 Subtype / genetics*
Influenza, Human / transmission
Influenza, Human / virology
Japan
Madin Darby Canine Kidney Cells
Morpholines / pharmacology*
Pyridones / pharmacology*
Triazines / pharmacology*
Viral Proteins / genetics*

Substances

Antiviral Agents
Dibenzothiepins
Morpholines
Pyridones
Triazines
Viral Proteins
baloxavir