Publication Date:
2013-07-12
Description:
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, 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.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3891892/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3891892/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Watanabe, Tokiko -- Kiso, Maki -- Fukuyama, Satoshi -- Nakajima, Noriko -- Imai, Masaki -- Yamada, Shinya -- Murakami, Shin -- Yamayoshi, Seiya -- Iwatsuki-Horimoto, Kiyoko -- Sakoda, Yoshihiro -- Takashita, Emi -- McBride, Ryan -- Noda, Takeshi -- Hatta, Masato -- Imai, Hirotaka -- Zhao, Dongming -- Kishida, Noriko -- Shirakura, Masayuki -- de Vries, Robert P -- Shichinohe, Shintaro -- Okamatsu, Masatoshi -- Tamura, Tomokazu -- Tomita, Yuriko -- Fujimoto, Naomi -- Goto, Kazue -- Katsura, Hiroaki -- Kawakami, Eiryo -- Ishikawa, Izumi -- Watanabe, Shinji -- Ito, Mutsumi -- Sakai-Tagawa, Yuko -- Sugita, Yukihiko -- Uraki, Ryuta -- Yamaji, Reina -- Eisfeld, Amie J -- Zhong, Gongxun -- Fan, Shufang -- Ping, Jihui -- Maher, Eileen A -- Hanson, Anthony -- Uchida, Yuko -- Saito, Takehiko -- Ozawa, Makoto -- Neumann, Gabriele -- Kida, Hiroshi -- Odagiri, Takato -- Paulson, James C -- Hasegawa, Hideki -- Tashiro, Masato -- Kawaoka, Yoshihiro -- AI058113/AI/NIAID NIH HHS/ -- AI099274/AI/NIAID NIH HHS/ -- HHSN266200700010C/AI/NIAID NIH HHS/ -- HHSN266200700010C/PHS HHS/ -- T32 AI078985/AI/NIAID NIH HHS/ -- England -- Nature. 2013 Sep 26;501(7468):551-5. doi: 10.1038/nature12392. Epub 2013 Jul 10.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉ERATO Infection-Induced Host Responses Project, Japan Science and Technology Agency, Saitama 332-0012, Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23842494" target="_blank"〉PubMed〈/a〉
Keywords:
Animals
;
Antiviral Agents/pharmacology
;
Cells, Cultured
;
Chickens/virology
;
DNA-Directed RNA Polymerases/antagonists & inhibitors
;
Dogs
;
Enzyme Inhibitors/pharmacology
;
Female
;
Ferrets/virology
;
Humans
;
Influenza A Virus, H1N1 Subtype/drug effects/enzymology
;
*Influenza A virus/chemistry/drug effects/isolation & purification/pathogenicity
;
Influenza, Human/drug therapy/*virology
;
Macaca fascicularis/virology
;
Madin Darby Canine Kidney Cells
;
Male
;
Mice
;
Mice, Inbred BALB C
;
Models, Molecular
;
Monkey Diseases/pathology/virology
;
Neuraminidase/antagonists & inhibitors
;
Orthomyxoviridae Infections/pathology/transmission/*virology
;
Quail/virology
;
Swine/virology
;
Swine, Miniature/virology
;
*Virus Replication/drug effects
Print ISSN:
0028-0836
Electronic ISSN:
1476-4687
Topics:
Biology
,
Chemistry and Pharmacology
,
Medicine
,
Natural Sciences in General
,
Physics
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