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	Prevailing pa mutation k356r in avian influenza h9n2 virus increases mammalian replication and pathogenicity
	Xu, Guanlong1,2; Zhang, Xuxiao1,2; Gao, Weihua1,2; Wang, Chenxi1,2; Wang, Jinliang1,2; Sun, Honglei1,2; Sun, Yipeng1,2; Guo, Lu3; Zhang, Rui1,2; Chang, Kin-Chow4
刊名	Journal of virology
	2016-09-01
卷号	90期号:18页码:8105-8114
ISSN号	0022-538X
DOI	10.1128/jvi.00883-16
通讯作者	Pu, juan(pujuan@cau.edu.cn)
英文摘要	Adaptation of the viral polymerase complex comprising pb1, pb2, and pa is necessary for efficient influenza a virus replication in new host species. we found that pa mutation k356r (pa-k356r) has become predominant since 2014 in avian h9n2 viruses in china as with seasonal human h1n1 viruses. the same mutation is also found in most human isolates of emergent avian h7n9 and h10n8 viruses whose six internal gene segments are derived from the h9n2 virus. we further demonstrated the mammalian adaptive functionality of the pa-k356r mutation. avian h9n2 virus with the pa-k356r mutation in human a549 cells showed increased nuclear accumulation of pa and increased viral polymerase activity that resulted in elevated levels of viral transcription and virus output. the same mutant virus in mice also enhanced virus replication and caused lethal infection. in addition, combined mutation of pa-k356r and pb2-e627k, a well-known mammalian adaptive marker, in the h9n2 virus showed further cooperative increases in virus production and severity of infection in vitro and in vivo. in summary, pa-k356r behaves as a novel mammalian tropism mutation, which, along with other mutations such as pb2-e627k, might render avian h9n2 viruses adapted for human infection. importance mutations of the polymerase complex (pb1, pb2, and pa) of influenza a virus are necessary for viral adaptation to new hosts. this study reports a novel and predominant mammalian adaptive mutation, pa-k356r, in avian h9n2 viruses and human isolates of emergent h7n9 and h10n8 viruses. we found that pa-356r in h9n2 viruses causes significant increases in virus replication and severity of infection in human cells and mice and that pa-k356r cooperates with the pb2-e627k mutation, a well-characterized human adaptive marker, to exacerbate mammalian infection in vitro and in vivo. therefore, the pa-k356r mutation is a significant adaptation in h9n2 viruses and related h7n9 and h10n8 reassortants toward human infectivity.
WOS关键词	INNATE IMMUNE-RESPONSE ; AMINO-ACID CHANGES ; A VIRUS ; POLYMERASE COMPLEX ; HIGH VIRULENCE ; HUMAN-CELLS ; H7N9 VIRUS ; INFECTIONS ; HEMAGGLUTININ ; MICE
WOS研究方向	Virology
WOS类目	Virology
语种	英语
出版者	AMER SOC MICROBIOLOGY
WOS记录号	WOS:000382314100008
内容类型	期刊论文
URI标识	http://www.corc.org.cn/handle/1471x/2375577
专题	中国科学院大学
通讯作者	Pu, Juan
作者单位	1.China Agr Univ, Key Lab Anim Epidemiol & Zoonosis, Minist Agr, Coll Vet Med, Beijing, Peoples R China 2.China Agr Univ, State Key Lab Agrobiotechnol, Beijing, Peoples R China 3.Chinese Acad Sci, Natl Key Lab Biomacromol, Univ Chinese Acad Sci, Inst Biophys, Beijing, Peoples R China 4.Univ Nottingham, Sch Vet Med & Sci, Sutton Bonington Campus, Loughborough, Leics, England
推荐引用方式 GB/T 7714	Xu, Guanlong,Zhang, Xuxiao,Gao, Weihua,et al. Prevailing pa mutation k356r in avian influenza h9n2 virus increases mammalian replication and pathogenicity[J]. Journal of virology,2016,90(18):8105-8114.
APA	Xu, Guanlong.,Zhang, Xuxiao.,Gao, Weihua.,Wang, Chenxi.,Wang, Jinliang.,...&Pu, Juan.(2016).Prevailing pa mutation k356r in avian influenza h9n2 virus increases mammalian replication and pathogenicity.Journal of virology,90(18),8105-8114.
MLA	Xu, Guanlong,et al."Prevailing pa mutation k356r in avian influenza h9n2 virus increases mammalian replication and pathogenicity".Journal of virology 90.18(2016):8105-8114.

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