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Emergence of H7N9 Influenza A Virus Resistant to Neuraminidase Inhibitors in Nonhuman Primates

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Title: Emergence of H7N9 Influenza A Virus Resistant to Neuraminidase Inhibitors in Nonhuman Primates
Authors: Itoh, Yasushi Browse this author →KAKEN DB
Shichinohe, Shintaro Browse this author →KAKEN DB
Nakayama, Misako Browse this author →KAKEN DB
Igarashi, Manabu Browse this author →KAKEN DB
Ishii, Akihiro Browse this author →KAKEN DB
Ishigaki, Hirohito Browse this author →KAKEN DB
Ishida, Hideaki Browse this author
Kitagawa, Naoko Browse this author
Sasamura, Takako Browse this author
Shiohara, Masanori Browse this author
Doi, Michiko Browse this author
Tsuchiya, Hideaki Browse this author →KAKEN DB
Nakamura, Shinichiro Browse this author →KAKEN DB
Okamatsu, Masatoshi Browse this author →KAKEN DB
Sakoda, Yoshihiro Browse this author →KAKEN DB
Kida, Hiroshi Browse this author →KAKEN DB
Ogasawara, Kazumasa Browse this author →KAKEN DB
Issue Date: Aug-2015
Publisher: American Society for Microbiology
Journal Title: Antimicrobial agents and chemotherapy
Volume: 59
Issue: 8
Start Page: 4962
End Page: 4973
Publisher DOI: 10.1128/AAC.00793-15
PMID: 26055368
Abstract: The number of patients infected with H7N9 influenza virus has been increasing since 2013. We examined the efficacy of neuraminidase (NA) inhibitors and the efficacy of a vaccine against an H7N9 influenza virus, A/Anhui/1/2013 (H7N9), isolated from a patient in a cynomolgus macaque model. NA inhibitors (oseltamivir and peramivir) barely reduced the total virus amount because of the emergence of resistant variants with R289K or I219T in NA [residues 289 and 219 in N9 of A/Anhui/1/2013 (H7N9) correspond to 292 and 222 in N2, respectively] in three of the six treated macaques, whereas subcutaneous immunization of an inactivated vaccine derived from A/duck/Mongolia/119/2008 (H7N9) prevented propagation of A/Anhui/1/2013 (H7N9) in all vaccinated macaques. The percentage of macaques in which variant H7N9 viruses with low sensitivity to the NA inhibitors were detected was much higher than that of macaques in which variant H5N1 highly pathogenic influenza virus was detected after treatment with one of the NA inhibitors in our previous study. The virus with R289K in NA was reported in samples from human patients, whereas that with I219T in NA was identified for the first time in this study using macaques, though no variant H7N9 virus was reported in previous studies using mice. Therefore, the macaque model enables prediction of the frequency of emerging H7N9 virus resistant to NA inhibitors in vivo. Since H7N9 strains resistant to NA inhibitors might easily emerge compared to other influenza viruses, monitoring of the emergence of variants is required during treatment of H7N9 influenza virus infection with NA inhibitors.
Type: article
Appears in Collections:獣医学院・獣医学研究院 (Graduate School of Veterinary Medicine / Faculty of Veterinary Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
国際連携研究教育局 : GI-CoRE (Global Institution for Collaborative Research and Education : GI-CoRE) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

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