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

被引:141
作者
Imai, Masaki [1 ]
Watanabe, Tokiko [1 ]
Kiso, Maki [1 ]
Nakajima, Noriko [2 ]
Yamayoshi, Seiya [1 ]
Iwatsuki-Horimoto, Kiyoko [1 ]
Hatta, Masato [3 ]
Yamada, Shinya [1 ]
Ito, Mutsumi [1 ]
Sakai-Tagawa, Yuko [1 ]
Shirakura, Masayuki [4 ]
Takashita, Emi [4 ]
Fujisaki, Seiichiro [4 ]
McBride, Ryan [5 ,6 ]
Thompson, Andrew J. [5 ,6 ]
Takahashi, Kenta [2 ]
Maemura, Tadashi [1 ]
Mitake, Hiromichi [1 ]
Chiba, Shiho [3 ]
Zhong, Gongxun [3 ]
Fan, Shufang [3 ]
Oishi, Kohei [1 ]
Yasuhara, Atsuhiro [1 ]
Takada, Kosuke [1 ]
Nakao, Tomomi [1 ]
Fukuyama, Satoshi [1 ]
Yamashita, Makoto [1 ]
Lopes, Tiago J. S. [1 ,3 ]
Neumann, Gabriele [3 ]
Odagiri, Takato [4 ]
Watanabe, Shinji [4 ]
Shu, Yuelong [7 ]
Paulson, James C. [5 ,6 ]
Hasegawa, Hideki [2 ]
Kawaoka, Yoshihiro [1 ,3 ,8 ]
机构
[1] Univ Tokyo, Inst Med Sci, Dept Microbiol & Immunol, Div Virol,Minato Ku, Tokyo 1088639, Japan
[2] Natl Inst Infect Dis, Dept Pathol, Shinjuku Ku, Tokyo 1628640, Japan
[3] Univ Wisconsin, Sch Vet Sci, Dept Pathobiol Sci, Influenza Res Inst, Madison, WI 53711 USA
[4] Natl Inst Infect Dis, Influenza Virus Res Ctr, Tokyo 2080011, Japan
[5] Scripps Res Inst, Dept Mol Med, La Jolla, CA 92037 USA
[6] Scripps Res Inst, Dept Immunol & Microbiol, La Jolla, CA 92037 USA
[7] China Ctr Dis Control & Prevent, Natl Inst Viral Dis Control & Prevent, Beijing 102206, Peoples R China
[8] Univ Tokyo, Inst Med Sci, Int Res Ctr Infect Dis, Dept Special Pathogens,Minato Ku, Tokyo 1088639, Japan
关键词
MULTIBASIC CLEAVAGE SITE; RECEPTOR-BINDING; AIRBORNE TRANSMISSION; MOLECULAR-BASIS; IN-VITRO; A VIRUS; H5N1; HEMAGGLUTININ; REPLICATION; SPECIFICITY;
D O I
10.1016/j.chom.2017.09.008
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
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.
引用
收藏
页码:615 / +
页数:20
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