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

• Published in: Cell host & microbe Vol. 22; no. 5; pp. 615 - 626.e8
• Main Authors: Imai, Masaki, Watanabe, Tokiko, Kiso, Maki, Nakajima, Noriko, Yamayoshi, Seiya, Iwatsuki-Horimoto, Kiyoko, Hatta, Masato, Yamada, Shinya, Ito, Mutsumi, Sakai-Tagawa, Yuko, Shirakura, Masayuki, Takashita, Emi, Fujisaki, Seiichiro, McBride, Ryan, Thompson, Andrew J., Takahashi, Kenta, Maemura, Tadashi, Mitake, Hiromichi, Chiba, Shiho, Zhong, Gongxun, Fan, Shufang, Oishi, Kohei, Yasuhara, Atsuhiro, Takada, Kosuke, Nakao, Tomomi, Fukuyama, Satoshi, Yamashita, Makoto, Lopes, Tiago J.S., Neumann, Gabriele, Odagiri, Takato, Watanabe, Shinji, Shu, Yuelong, Paulson, James C., Hasegawa, Hideki, Kawaoka, Yoshihiro
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 08.11.2017
• Subjects: Animals; Antiviral Agents - pharmacology; antiviral sensitivity; Brain - pathology; Brain - virology; Cell Line; Chickens - virology; Conjunctiva - pathology; Conjunctiva - virology; Disease Models, Animal; Enzyme Inhibitors - pharmacology; ferrets; Ferrets - virology; highly pathogenic avian influenza H7N9 viruses; Humans; Influenza A Virus, H7N9 Subtype - isolation & purification; Influenza A Virus, H7N9 Subtype - pathogenicity; Influenza in Birds - virology; Lung - pathology; Lung - virology; Macaca - virology; Mice; Neuraminidase - drug effects; nonhuman primates; Orthomyxoviridae Infections - pathology; Orthomyxoviridae Infections - transmission; Orthomyxoviridae Infections - virology; pathogenicity; receptor-binding specificity; replication capacity; Respiratory Tract Infections - pathology; Respiratory Tract Infections - virology; transmissibility; Virus Replication; antiviral sensitivity; pathogenicity; receptor-binding specificity; ferrets; transmissibility; replication capacity; nonhuman primates; highly pathogenic avian influenza H7N9 viruses; mice
• ISSN: 1931-3128; 1934-6069; 1934-6069
• DOI: 10.1016/j.chom.2017.09.008

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. [Display omitted] •Highly pathogenic avian influenza (HPAI) H7N9 viruses replicate efficiently in mammals•HPAI H7N9 viruses are more pathogenic than low pathogenic H7N9 viruses in mammals•HPAI H7N9 viruses transmit via respiratory droplets among ferrets•HPAI H7N9 viruses show low sensitivity to neuraminidase inhibitors in mice 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.