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Natural variant R246K in hemagglutinin increased zoonotic characteristics and renal inflammation in mice infected with H9N2 influenza virus

文献类型： 外文期刊

作者： Liu, Yang 1 ; Zeng, Qinghang 1 ; Hu, Xinyu 1 ; Xu, Zhihong 1 ; Pan, Chungen 6 ; Liu, Quan 1 ; Yu, Jieshi 7 ; Wu, Siyu 7 ; Sun, Minhua 1 ; Liao, Ming 1 ;

作者机构： 1.Inst Anim Hlth, Guangdong Acad Agr Sci, Guangzhou, Peoples R China

2.Guangdong Lab Lingnan Modern Agr, Guangzhou, Peoples R China

3.Zhongkai Univ Agr & Engn, Coll Anim Sci & Technol, Guangzhou, Peoples R China

4.Minist Agr & Rural Affairs, Key Lab Prevent & Control Avian Influenza & Other, Guangzhou, Peoples R China

5.Key Lab Livestock Dis Prevent Guangdong Prov, Guangzhou, Peoples R China

6.Guangdong HaidGroup Co Ltd, Haid Res Inst, Guangzhou, Peoples R China

7.Guangdong Acad Agr Sci, Agrobiol Gene Res Ctr, Guangzhou, Peoples R China

关键词： Avian influenza virus; Hemagglutinin; Variation; Zoonotic; Pandemic

期刊名称：VETERINARY MICROBIOLOGY （ 影响因子：3.3； 五年影响因子：3.5 ）

ISSN： 0378-1135

年卷期： 2023 年 279 卷

页码：

收录情况： SCI

摘要： Considered a potential pandemic candidate, the widespread among poultry of H9N2 avian influenza viruses across Asia and North Africa pose an increasing threat to poultry and human health. The massive epidemic of H9N2 viruses has expanded the host range; however, the molecular basis and characteristic underlying the transmission to poultry and mammals remains unclear. Our previous study has proved that some natural mu-tations in the HA gene enhanced the binding ability of the H9N2 virus to alpha-2,6 SA receptors. Here, we sys-tematically analyzed the impact of these natural mutations on zoonotic characteristics and the pathogenicity of H9N2 AIVs in poultry and mammals. Our study demonstrated that mutation R246K increased the replication in human lung epithelial cells in vitro. Mutation R246K increased the virus shedding of oropharyngeal swabs during early-stage infection in chickens. Moreover, mutation R246K displayed stronger pH stability and pathogenicity in mice. The strong renal tropism and inflammatory response may accelerate the pathogenicity. In summary, we found that natural variation R246K in HA of prevalent H9N2 in China promoted the transmissibility in chicken and accelerate the pathogenicity in mice, posing a great concern for zoonotic and pandemic emergence.

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