Adaptive amino acid substitutions enable transmission of an H9N2 avian influenza virus in guinea pigs

文献类型: 外文期刊

第一作者: Liu Lina

作者: Liu Lina;Lu Yuefeng;Li Jiakai;Zhang Jianhui;Luo Qingping;Zhang Wenting;Shang Yu;Wang Honglin;Zhang Tengfei;Wen Guoyuan;Shao Huabin;Zhao Zongzheng;Wang Chengyu;Guo Zhendong;Zhang Chunmao;Gao Yuwei;Zhao Zongzheng;Chen Saijuan;Dong Shishan;Chen Ligong;Guo Kangkang;Jin Meilin;Zhu Jiping

作者机构:

期刊名称:SCIENTIFIC REPORTS ( 影响因子:4.379; 五年影响因子:5.133 )

ISSN: 2045-2322

年卷期: 2019 年 9 卷

页码:

收录情况: SCI

摘要: H9N2 is the most prevalent low pathogenic avian influenza virus (LPAIV) in domestic poultry in the world. Two distinct H9N2 poultry lineages, G1-like (A/quail/Hong Kong/G1/97) and Y280-like (A/Duck/Hong Kong/Y280/1997) viruses, are usually associated with binding affinity for both alpha 2,3 and alpha 2,6 sialic acid receptors (avian and human receptors), raising concern whether these viruses possess pandemic potential. To explore the impact of mouse adaptation on the transmissibility of aY280-like virus A/Chicken/Hubei/214/2017(H9N2) (abbreviated as WT), we performed serial lung-to-lung passages of the WT virus in mice. The mouse-adapted variant (MA) exhibited enhanced pathogenicity and advantaged transmissibility after passaging in mice. Sequence analysis of the complete genomes of the MA virus revealed a total of 16 amino acid substitutions. These mutations distributed across 7 segments including PB2, PB1, PA, NP, HA, NA and NS1 genes. Furthermore, we generated a panel of recombinant or mutant H9N2 viruses using reverse genetics technology and confirmed that the PB2 gene governing the increased pathogenicity and transmissibility. The combinations of 340 K and 588V in PB2 were important in determining the altered features. Our findings elucidate the specific mutations in PB2 contribute to the phenotype differences and emphasize the importance of monitoring the identified amino acid substitutions due to their potential threat to human health.

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