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Nature. Characterization of H7N9 influenza A viruses isolated from humans

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  • Nature. Characterization of H7N9 influenza A viruses isolated from humans

    [Source: Nature, full page: (LINK). Abstract, edited.]

    Nature | Letter

    Characterization of H7N9 influenza A viruses isolated from humans

    Tokiko Watanabe,<SUP>1, 15 </SUP>Maki Kiso,<SUP>2, 15 </SUP>Satoshi Fukuyama,<SUP>1, 15 </SUP>Noriko Nakajima,<SUP>3, 15 </SUP>Masaki Imai,<SUP>4, 15 </SUP>Shinya Yamada,<SUP>2 </SUP>Shin Murakami,<SUP>5 </SUP>Seiya Yamayoshi,<SUP>2 </SUP>Kiyoko Iwatsuki-Horimoto,<SUP>2 </SUP>Yoshihiro Sakoda,<SUP>6 </SUP>Emi Takashita,<SUP>4 </SUP>Ryan McBride,<SUP>7 </SUP>Takeshi Noda,<SUP>2 </SUP>Masato Hatta,<SUP>8 </SUP>Hirotaka Imai,<SUP>8 </SUP>Dongming Zhao,<SUP>1 </SUP>Noriko Kishida,<SUP>4 </SUP>Masayuki Shirakura,<SUP>4 </SUP>Robert P. de Vries,<SUP>7 </SUP>Shintaro Shichinohe,<SUP>6 </SUP>Masatoshi Okamatsu,<SUP>6 </SUP>Tomokazu Tamura,<SUP>6 </SUP>Yuriko Tomita,<SUP>1 </SUP>Naomi Fujimoto,<SUP>1 </SUP>Kazue Goto,<SUP>1 </SUP>Hiroaki Katsura,<SUP>2 </SUP>Eiryo Kawakami,<SUP>1 </SUP>Izumi Ishikawa,<SUP>1 </SUP>Shinji Watanabe,<SUP>1, 9 </SUP>Mutsumi Ito,<SUP>2 </SUP>Yuko Sakai-Tagawa,<SUP>2 </SUP>Yukihiko Sugita,<SUP>2 </SUP>Ryuta Uraki,<SUP>2 </SUP>Reina Yamaji,<SUP>2 </SUP>Amie J. Eisfeld,<SUP>8 </SUP>Gongxun Zhong,<SUP>8 </SUP>Shufang Fan,<SUP>8 </SUP>Jihui Ping,<SUP>8 </SUP>Eileen A. Maher,<SUP>8 </SUP>Anthony Hanson,<SUP>8 </SUP>Yuko Uchida,<SUP>10 </SUP>Takehiko Saito,<SUP>10 </SUP>Makoto Ozawa,<SUP>11, 12 </SUP>Gabriele Neumann,<SUP>8 </SUP>Hiroshi Kida,<SUP>6, 13 </SUP>Takato Odagiri,<SUP>4 </SUP>James C. Paulson,<SUP>7 </SUP>Hideki Hasegawa,<SUP>3 </SUP>Masato Tashiro<SUP>4 </SUP>& Yoshihiro Kawaoka<SUP>1, 2, 5, 8, 14</SUP>
    Journal name: Nature - Year published: (2013)

    DOI: doi:10.1038/nature12392

    Received 23 May 2013 - Accepted 20 June 2013 - Published online 10 July 2013

    Avian influenza A viruses rarely infect humans; however, when human infection and subsequent human-to-human transmission occurs, worldwide outbreaks (pandemics) can result. The recent sporadic infections of humans in China with a previously unrecognized avian influenza A virus of the H7N9 subtype (A(H7N9)) have caused concern owing to the appreciable case fatality rate associated with these infections (more than 25%), potential instances of human-to-human transmission<SUP>1</SUP>, and the lack of pre-existing immunity among humans to viruses of this subtype. Here we characterize two early human A(H7N9) isolates, A/Anhui/1/2013 (H7N9) and A/Shanghai/1/2013 (H7N9); hereafter referred to as Anhui/1 and Shanghai/1, respectively. In mice, Anhui/1 and Shanghai/1 were more pathogenic than a control avian H7N9 virus (A/duck/Gunma/466/2011 (H7N9); Dk/GM466) and a representative pandemic 2009 H1N1 virus (A/California/4/2009 (H1N1pdm09); CA04). Anhui/1, Shanghai/1 and Dk/GM466 replicated well in the nasal turbinates of ferrets. In nonhuman primates, Anhui/1 and Dk/GM466 replicated efficiently in the upper and lower respiratory tracts, whereas the replicative ability of conventional human influenza viruses is typically restricted to the upper respiratory tract of infected primates. By contrast, Anhui/1 did not replicate well in miniature pigs after intranasal inoculation. Critically, Anhui/1 transmitted through respiratory droplets in one of three pairs of ferrets. Glycan arrays showed that Anhui/1, Shanghai/1 and A/Hangzhou/1/2013 (H7N9) (a third human A(H7N9) virus tested in this assay) bind to human virus-type receptors, a property that may be critical for virus transmissibility in ferrets. Anhui/1 was found to be less sensitive in mice to neuraminidase inhibitors than a pandemic H1N1 2009 virus, although both viruses were equally susceptible to an experimental antiviral polymerase inhibitor. The robust replicative ability in mice, ferrets and nonhuman primates and the limited transmissibility in ferrets of Anhui/1 suggest that A(H7N9) viruses have pandemic potential.