Adaptive amino acid substitutions enable transmission of an H9N2 avian influenza virus in guinea pigs
文献类型: 外文期刊
作者: Liu Lina 1 ; Chen Saijuan 3 ; Wang Chengyu 2 ; Lu Yuefeng 1 ; Dong Shishan 3 ; Chen Ligong 3 ; Guo Kangkang 3 ; Guo Zhend 1 ;
作者机构: 1.Hubei Acad Agr Sci, Inst Anim Husb & Vet Sci, Wuhan, Peoples R China
2.Acad Mil Med Sci, Inst Mil Vet, 666 West Liuying Rd, Changchun 130122, Jilin, Peoples R China
3.Hebei Agr Univ, Coll Vet Med, Inst Mt Area Res, Baoding 071001, Hebei, Peoples R China
4.Huazhong Agr Univ, Coll Vet Med, Wuhan, Peoples R China
5.Wuhan Univ Bioengn, Hubei Engn Res Ctr Viral Vector, Wuhan 430415, Peoples R China
期刊名称:SCIENTIFIC REPORTS ( 2020影响因子:4.379; 五年影响因子:5.133 )
ISSN: 2045-2322
年卷期: 2019 年 9 卷
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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