A Highly Pathogenic Avian H7N9 Influenza Virus Isolated from A Human Is Lethal in Some Ferrets Infected via Respiratory Droplets

Masaki Imai, Tokiko Watanabe, Maki Kiso, Noriko Nakajima, Seiya Yamayoshi, Kiyoko Iwatsuki-Horimoto, Masato Hatta, Shinya Yamada, Mutsumi Ito, Yuko Sakai-Tagawa, Masayuki Shirakura, Emi Takashita, Seiichiro Fujisaki, Ryan McBride, Andrew J. Thompson, Kenta Takahashi, Tadashi Maemura, Hiromichi Mitake, Shiho Chiba, Gongxun ZhongShufang Fan, Kohei Oishi, Atsuhiro Yasuhara, Kosuke Takada, Tomomi Nakao, Satoshi Fukuyama, Makoto Yamashita, Tiago J.S. Lopes, Gabriele Neumann, Takato Odagiri, Shinji Watanabe, Yuelong Shu, James C. Paulson, Hideki Hasegawa, Yoshihiro Kawaoka

Research output: Contribution to journalArticlepeer-review

115 Scopus citations

Abstract

Low pathogenic H7N9 influenza viruses have recently evolved to become highly pathogenic, raising concerns of a pandemic, particularly if these viruses acquire efficient human-to-human transmissibility. We compared a low pathogenic H7N9 virus with a highly pathogenic isolate, and two of its variants that represent neuraminidase inhibitor-sensitive and -resistant subpopulations detected within the isolate. The highly pathogenic H7N9 viruses replicated efficiently in mice, ferrets, and/or nonhuman primates, and were more pathogenic in mice and ferrets than the low pathogenic H7N9 virus, with the exception of the neuraminidase inhibitor-resistant virus, which showed mild-to-moderate attenuation. All viruses transmitted among ferrets via respiratory droplets, and the neuraminidase-sensitive variant killed several of the infected and exposed animals. Neuraminidase inhibitors showed limited effectiveness against these viruses in vivo, but the viruses were susceptible to a polymerase inhibitor. These results suggest that the highly pathogenic H7N9 virus has pandemic potential and should be closely monitored. Highly pathogenic avian influenza (HPAI) H7N9 viruses have emerged and raised concerns of a pandemic. Imai et al. characterized an HPAI H7N9 virus isolated from a human. This virus transmitted among ferrets without prior adaptation and caused lethal infection in animals, demonstrating its pandemic potential and the need for surveillance.

Original languageEnglish
Pages (from-to)615-626.e8
JournalCell Host and Microbe
Volume22
Issue number5
DOIs
StatePublished - 8 Nov 2017
Externally publishedYes

Keywords

  • antiviral sensitivity
  • ferrets
  • highly pathogenic avian influenza H7N9 viruses
  • mice
  • nonhuman primates
  • pathogenicity
  • receptor-binding specificity
  • replication capacity
  • transmissibility

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