Characterization of H7N9 influenza A viruses isolated from humans

被引：340

作者：

Watanabe, Tokiko ^{[1
]}

Kiso, Maki ^{[2
]}

Fukuyama, Satoshi ^{[1
]}

Nakajima, Noriko ^{[3
]}

Imai, Masaki ^{[4
]}

Yamada, Shinya ^{[2
]}

Murakami, Shin ^{[5
]}

Yamayoshi, Seiya ^{[2
]}

Iwatsuki-Horimoto, Kiyoko ^{[2
]}

Sakoda, Yoshihiro ^{[6
]}

Takashita, Emi ^{[4
]}

McBride, Ryan ^{[7
]}

Noda, Takeshi ^{[2
]}

Hatta, Masato ^{[8
]}

Imai, Hirotaka ^{[8
]}

Zhao, Dongming ^{[1
]}

Kishida, Noriko ^{[4
]}

Shirakura, Masayuki ^{[4
]}

de Vries, Robert P. ^{[7
]}

Shichinohe, Shintaro ^{[6
]}

Okamatsu, Masatoshi ^{[6
]}

Tamura, Tomokazu ^{[6
]}

Tomita, Yuriko ^{[1
]}

Fujimoto, Naomi ^{[1
]}

Goto, Kazue ^{[1
]}

Katsura, Hiroaki ^{[2
]}

Kawakami, Eiryo ^{[1
]}

Ishikawa, Izumi ^{[1
]}

Watanabe, Shinji ^{[1
,9
]}

Ito, Mutsumi ^{[2
]}

Sakai-Tagawa, Yuko ^{[2
]}

Sugita, Yukihiko ^{[2
]}

Uraki, Ryuta ^{[2
]}

Yamaji, Reina ^{[2
]}

Eisfeld, Amie J. ^{[8
]}

Zhong, Gongxun ^{[8
]}

Fan, Shufang ^{[8
]}

Ping, Jihui ^{[8
]}

Maher, Eileen A. ^{[8
]}

Hanson, Anthony ^{[8
]}

Uchida, Yuko ^{[10
]}

Saito, Takehiko ^{[10
]}

Ozawa, Makoto ^{[11
,12
]}

Neumann, Gabriele ^{[8
]}

Kida, Hiroshi ^{[6
,13
]}

Odagiri, Takato ^{[4
]}

Paulson, James C. ^{[7
]}

Hasegawa, Hideki ^{[3
]}

Tashiro, Masato ^{[4
]}

Kawaoka, Yoshihiro ^{[1
,2
,5
,8
,14
]}

机构：

[1] Japan Sci & Technol Agcy, ERATO Infect Induced Host Responses Project, Kawaguchi, Saitama 3320012, Japan

[2] Univ Tokyo, Inst Med Sci, Dept Microbiol & Immunol, Div Virol, Tokyo 1088639, Japan

[3] Natl Inst Infect Dis, Dept Pathol, Shinjuku Ku, Tokyo 1628640, Japan

[4] Natl Inst Infect Dis, Influenza Virus Res Ctr, Tokyo 2080011, Japan

[5] Univ Tokyo, Inst Med Sci, Int Res Ctr Infect Dis, Dept Special Pathogens,Minato Ku, Tokyo 1088639, Japan

[6] Hokkaido Univ, Grad Sch Vet Med, Dept Dis Control, Microbiol Lab, Sapporo, Hokkaido 0600818, Japan

[7] Scripps Res Inst, La Jolla, CA 92037 USA

[8] Univ Wisconsin, Sch Vet Med, Dept Pathobiol Sci, Madison, WI 53711 USA

[9] Miyazaki Univ, Dept Vet Sci, Lab Vet Microbiol, Miyazaki 8892192, Japan

[10] Natl Inst Anim Hlth, Influenza & Pr Dis Res Ctr, Tsukuba, Ibaraki 3050856, Japan

[11] Kagoshima Univ, Joint Fac Vet Med, Lab Anim Hyg, Kagoshima 8900065, Japan

[12] Kagoshima Univ, Joint Fac Vet Med, Transboundary Anim Dis Ctr, Kagoshima 8900065, Japan

[13] Hokkaido Univ, Res Ctr Zoonosis Control, Sapporo, Hokkaido 0010020, Japan

[14] Kyoto Univ, Inst Virus Res, Dept Biol Responses, Lab Bioresponses Regulat, Kyoto 6068507, Japan

来源：

NATURE | 2013年 / 501卷 / 7468期

基金：

日本科学技术振兴机构;

关键词：

MOLECULAR-BASIS; AVIAN H5N1; IN-VITRO; TRANSMISSION; REPLICATION; INFECTION; BINDING; FERRETS; SITE; PATHOGENESIS;

D O I：

10.1038/nature12392

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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(1), 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.

引用

页码：551 / +

页数：7

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