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Emergence and Adaptation of a Novel Highly Pathogenic H7N9 Influenza Virus in Birds and Humans from a 2013 Human-Infecting Low-Pathogenic Ancestor

文献类型：期刊论文

作者Ren, Tao1,2,6; Lao, Guangjie2; Xu, Chenggang1,2,6; Xu, Bing11; Liu, Wenjun7; Zhang, Guihong1,2,6; Holmes, Edward C.9,10; Cui, Jie4; Shi, Weifeng5; Gao, George F.3,7,14
刊名JOURNAL OF VIROLOGY
出版日期2018
卷号92期号:2页码:12
ISSN号0022-538X
关键词emergence adaptation highly pathogenic H7N9 influenza virus multiple basic amino acids
DOI10.1128/JVI.00921-17
英文摘要Since its emergence in 2013, the H7N9 low-pathogenic avian influenza virus (LPAIV) has been circulating in domestic poultry in China, causing five waves of human infections. A novel H7N9 highly pathogenic avian influenza virus (HPAIV) variant possessing multiple basic amino acids at the cleavage site of the hemagglutinin (HA) protein was first reported in two cases of human infection in January 2017. More seriously, those novel H7N9 HPAIV variants have been transmitted and caused outbreaks on poultry farms in eight provinces in China. Herein, we demonstrate the presence of three different amino acid motifs at the cleavage sites of these HPAIV variants which were isolated from chickens and humans and likely evolved from the preexisting LPAIVs. Animal experiments showed that these novel H7N9 HPAIV variants are both highly pathogenic in chickens and lethal to mice. Notably, humanorigin viruses were more pathogenic in mice than avian viruses, and the mutations in the PB2 gene associated with adaptation to mammals (E627K, A588V, and D701N) were identified by next-generation sequencing (NGS) and Sanger sequencing of the isolates from infected mice. No polymorphisms in the key amino acid substitutions of PB2 and HA in isolates from infected chicken lungs were detected by NGS. In sum, these results highlight the high degree of pathogenicity and the valid transmissibility of this new H7N9 variant in chickens and the quick adaptation of this new H7N9 variant to mammals, so the risk should be evaluated and more attention should be paid to this variant. IMPORTANCE Due to the recent increased numbers of zoonotic infections in poultry and persistent human infections in China, influenza A(H7N9) virus has remained a public health threat. Most of the influenza A(H7N9) viruses reported previously have been of low pathogenicity. Now, these novel H7N9 HPAIV variants have caused human infections in three provinces and outbreaks on poultry farms in eight provinces in China. We analyzed the molecular features and compared the relative characteristics of one H7N9 LPAIV and two H7N9 HPAIVs isolated from chickens and two human-origin H7N9 HPAIVs in chicken and mouse models. We found that all HPAIVs both are highly pathogenic and have valid transmissibility in chickens. Strikingly, the human-origin viruses were more highly pathogenic than the avian-origin viruses in mice, and dynamic mutations were confirmed by NGS and Sanger sequencing. Our findings offer important insight into the origin, adaptation, pathogenicity, and transmissibility of these viruses to both poultry and mammals.
资助项目National Natural Science Foundation (NSFC) of China[31672586] ; National Natural Science Foundation (NSFC) of China[U1501212] ; National Natural Science Foundation (NSFC) of China[31471253] ; National Natural Science Foundation (NSFC) of China[81470096] ; Science and Technology Planning Project of Guangdong Province[2013B020224] ; National Key Research and Development Program of China[2016YFC1200800] ; National Key Research and Development Program of China[2016YFD0500201] ; National Key Research and Development Program of China[2016YFD0500800] ; Special Support Plan of Guangdong Province in Science and Technology for Talents ; Taishan Scholar project of Shandong Province ; CAS Pioneer Hundred Talents Program ; National Program for Support of Top-Notch Young Professionals ; NHMRC Australia fellowship[GNT1037231] ; Youth Innovation Promotion Association of the Chinese Academy of Sciences (CAS)[2017122]
WOS研究方向Virology
语种英语
出版者AMER SOC MICROBIOLOGY
WOS记录号WOS:000419042000002
源URL[http://202.127.146.157/handle/2RYDP1HH/4377]  
专题中国科学院武汉植物园
通讯作者Gao, George F.; Liao, Ming
作者单位1.Key Lab Zoonoses Prevent & Control Guangdong Prov, Guangzhou, Guangdong, Peoples R China
2.South China Agr Univ, Coll Vet Med, Natl & Reg Joint Engn Lab Medicament Zoonoses Pre, Guangzhou, Guangdong, Peoples R China
3.Chinese Acad Sci, Ctr Influenza Res & Early Warning CASCIRE, Beijing, Peoples R China
4.Chinese Acad Sci, Wuhan Inst Virol, Ctr Emerging Infect Dis, CAS Key Lab Special Pathogens & Biosafety, Wuhan, Hubei, Peoples R China
5.Taishan Med Coll, Inst Pathogen Biol, Tai An, Shandong, Peoples R China
6.Minist Agr, Key Lab Anim Vaccine Dev, Key Lab Zoonoses, Guangzhou, Guangdong, Peoples R China
7.Chinese Acad Sci, Inst Microbiol, CAS Key Lab Pathogen Microbiol & Immunol, Beijing, Peoples R China
8.Guangzhou Med Univ, Guangzhou Peoples Hosp 8, Guangzhou, Guangdong, Peoples R China
9.Univ Sydney, Sch Life & Environm Sci, Charles Perkins Ctr, Marie Bashir Inst Infect Dis & Biosecur, Sydney, NSW, Australia
10.Univ Sydney, Sydney Med Sch, Sydney, NSW, Australia
推荐引用方式
GB/T 7714		 Ren, Tao,Lao, Guangjie,Xu, Chenggang,et al. Emergence and Adaptation of a Novel Highly Pathogenic H7N9 Influenza Virus in Birds and Humans from a 2013 Human-Infecting Low-Pathogenic Ancestor[J]. JOURNAL OF VIROLOGY,2018,92(2):12.
APA Ren, Tao.,Lao, Guangjie.,Xu, Chenggang.,Xu, Bing.,Liu, Wenjun.,...&Su, Guanming.(2018).Emergence and Adaptation of a Novel Highly Pathogenic H7N9 Influenza Virus in Birds and Humans from a 2013 Human-Infecting Low-Pathogenic Ancestor.JOURNAL OF VIROLOGY,92(2),12.
MLA Ren, Tao,et al."Emergence and Adaptation of a Novel Highly Pathogenic H7N9 Influenza Virus in Birds and Humans from a 2013 Human-Infecting Low-Pathogenic Ancestor".JOURNAL OF VIROLOGY 92.2(2018):12.

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