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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

引用

Virologica Sinica 2022年第1期37卷 38-47页

作者： 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 UniversityGuangzhou510642China National Avian Infiuenza Para-reference Laboratory South China Agricultural UniversityGuangzhou510642China Guangdong Laboratory for Lingnan Modern Agriculture Guangzhou510642China Gongbei Customs Technology Center Zhuhai519000China National and Regional Joint Engineering Laboratory for Medicament of Zoonoses Prevention and Control Guangzhou510642China Key Laboratory of Zoonoses Ministry of AgricultureGuangzhou510642China Key Laboratory of Animal Vaccine Development Ministry of AgricultureGuangzhou510642China Key Laboratory of Zoonoses Prevention and Control of Guangdong Province Guangzhou510642China

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 *** insertion of a“KRTA”motif at hemagglutinin cleavage site(HACS)occurred in the early stage of HP H7N9 *** the co-circulation,the HACS of HP-H7N9 variants were more polymorphic in birds and *** 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 *** results of bioinformatics analysis indicated that the PEVPKRKRTAR/G motif of HACS had become the dominant motif in ***,we generated six H7N9 viruses bearing the PEIPKGR/G,PEVPKGR/G,PEVPKRKRTAR/G,PEVPKGKRTAR/G,PEVPKGKRIAR/G,and PEVPKRKRR/G ***,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 *** contrast,the insertion of non-basic amino acid isoleucine and alanine(IA)decreased the transmissibility in chickens and virulence in ***,the I335V 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 *** ongoing evolution of H7N9 increasingly threatens public health and poultry industry,so,its comprehensive surveillance and prevention of H7N9 viruses should be pursued.

关键词： H7N9 Highly pathogenic Cleavage site basic and non-basic amino acids Pathogenicity

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