139D in NS1 Contributes to the Virulence of H5N6 Influenza Virus in Mice

被引：1
作者：
Huang, Kun [1 ,2 ,3 ]
Mao, Haiying [1 ,2 ,3 ]
Ren, Peilei [1 ,2 ,3 ]
Zhang, Yufei [1 ,2 ,3 ]
Sun, Xiaomei [1 ,2 ,3 ]
Zou, Zhong [1 ,2 ,3 ]
Jin, Meilin [1 ,2 ,3 ]
机构：
[1] Huazhong Agr Univ, State Key Lab Agr Microbiol, Wuhan, Peoples R China
[2] Huazhong Agr Univ, Coll Vet Med, Wuhan, Peoples R China
[3] Minist Agr, Key Lab Dev Vet Diagnost Prod, Wuhan, Peoples R China
来源：
FRONTIERS IN VETERINARY SCIENCE | 2022年 / 8卷
基金：
中国国家自然科学基金;
关键词：
virulence; mice; NS1; 139D; PROTEIN INDUCES APOPTOSIS; AMINO-ACID SUBSTITUTION; A-VIRUS; EVOLUTION; PATHOGENICITY; HEMAGGLUTININ; DETERMINANTS; ADAPTATION; INFECTION; SUBUNIT;
D O I：
10.3389/fvets.2021.808234
中图分类号：
S85 [动物医学（兽医学）];
学科分类号：
0906 ;
摘要：
H5N6, the highly pathogenic avian influenza A virus (IAV) of clade 2.3.4.4, causes global outbreaks in poultry. H5N6 has become the dominant IAV subtype in waterfowls and causes human infections with high mortality rates. Here, we isolated two strains of H5N6, XGD and JX, from chickens and ducks, respectively. Growth kinetics were evaluated in duck embryo fibroblasts, chicken embryo fibroblasts, Madin-Darby canine kidney cells, and A549 lung carcinoma cells. Receptor binding specificity was analyzed via sialic acid-binding activity assay. The virulence of each strain was tested in BALB/c mice, and recombinant viruses were constructed via reverse genetics to further analyze the pathogenicity. The two strains showed no significant differences in growth kinetics in vitro; however, JX was more virulent in mice than XGD. We also identified 13 mutations in six viral proteins of the two strains through genetic analysis. Our study showed that the NS1 protein played a crucial role in enhancing the virulence of JX. Specifically, the amino acid 139D in NS1 contributed to the high pathogenicity. Therefore, 139D in NS1 might provide insight into the underlying mechanism of IAV adaptation in mammals.
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页数：9
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