Since mid-2016,the low pathogenic H7N9 influenza virus has evolved into a highly pathogenic(HP)phenotype in China,raising many concerns about public health and poultry industry.The insertion of a"KRTA"motif at hemagglutinin cleavage site(HACS)occurred in the early stage of HP H7N9 variants.During the co-circulation,the HACS of HP-H7N9 variants were more polymorphic in birds and humans.Although HP-H7N9 variants,unlike the H5 subtype virus,exhibited the insertions of basic and non-basic amino acids,the underlying function of those insertions and substitutions remains unclear.The results of bioinformatics analysis indicated that the PEVPKRKRTAR/G motif of HACS had become the dominant motif in China.Then,we generated six H7N9 viruses bearing the PEIPKGR/G,PEVPKGR/G,PEVPKRKRTAR/G,PEVPKGKRTAR/G,PEVPKGKRIAR/G,and PEVPKRKRR/G motifs.Interestingly,after the deletion of threonine and alanine(TA)at HACS,the H7N9 viruses manifested decreased thermostability and virulence in mice,and the PEVPKRKRTAR/G-motif virus is prevalent in birds and humans probably due to its increased transmissibility and moderate virulence.By contrast,the insertion of non-basic amino acid isoleucine and alanine(IA)decreased the transmissibility in chickens and virulence in mice.Remarkably,the 1335V substitution of H7N9 virus enhanced infectivity and transmission in chickens,suggesting that the combination of mutations and insertions of amino acids at the HACS promoted replication and pathogenicity in chickens and mice.The ongoing evolution of H7N9 increasingly threatens public health and poultry industry,so,its comprehensive surveillance and prevention of H7N9 viruses should be pursued.

Aobaixue Zhou;Jiahao Zhang;Huanan Li;Qiang Xu;Yiqun Chen;Bo Li;Wanying Liu;Guanming Su;Xingxing Ren;Guangjie Lao;Baozheng Luo;Ming Liao;Wenbao Qi

College of Veterinary Medicine,South China Agricultural University,Guangzhou,510642,China;National Avian Influenza Para-reference Laboratory,South China Agricultural University,Guangzhou,510642,China;Gongbei Customs Technology Center,Zhuhai,519000,China;National and Regional Joint Engineering Laboratory for Medicament of Zoonoses Prevention and Control,Guangzhou,510642,China;Key Laboratory of Zoonoses,Ministry of Agriculture,Guangzhou,510642,China;Key Laboratory of Animal Vaccine Development,Ministry of Agriculture,Guangzhou,510642,China;Key Laboratory of Zoonoses Prevention and Control of Guangdong Province,Guangzhou,510642,China;Guangdong Laboratory for Lingnan Modern Agriculture,Guangzhou,510642,China

中国病毒学

[1]Aobaixue Zhou;Jiahao Zhang;Huanan Li;Qiang Xu;Yiqun Chen;Bo Li;Wanying Liu;Guanming Su;Xingxing Ren;Guangjie Lao;Baozheng Luo;Ming Liao;Wenbao Qi-.Combined insertion of basic and non-basic amino acids at hemagglutinin cleavage site of highly pathogenic H7N9 virus promotes replication and pathogenicity in chickens and mice)[J].中国病毒学,2022(01):38-47

KRTA,PEVPKRKRTAR,PEIPKGR,PEVPKGR,PEVPKGKRTAR,PEVPKGKRIAR,PEVPKRKRR,1335V

Combined,basic,amino,acids,hemagglutinin,cleavage,site,highly,H7N9,promotes,replication,pathogenicity,chickens,mice,Since,mid,low,influenza,has,evolved,into,HP,phenotype,China,raising,many,concerns,about,public,health,poultry,industry,HACS,occurred,early,stage,variants,During,circulation,were,more,polymorphic,birds,humans,Although,unlike,H5,subtype,exhibited,insertions,underlying,function,those,substitutions,remains,unclear,results,bioinformatics,analysis,indicated,that,had,become,dominant,Then,generated,six,viruses,bearing,motifs,Interestingly,after,deletion,threonine,alanine,manifested,decreased,thermostability,virulence,prevalent,probably,due,its,increased,transmissibility,moderate,By,contrast,isoleucine,Remarkably,enhanced,infectivity,transmission,suggesting,combination,mutations,promoted,ongoing,evolution,increasingly,threatens,comprehensive,surveillance,prevention,should,pursued

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