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

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Sci Rep. 2019 Dec 24;9(1):19734. doi: 10.1038/s41598-019-56122-6. Adaptive amino acid substitutions enable transmission of an H9N2 avian influenza virus in guinea pigs.

Lina L¹, Saijuan C², Chengyu W³, Yuefeng L¹, Shishan D², Ligong C², Kangkang G², Zhendong G³, Jiakai L¹, Jianhui Z¹, Qingping L¹, Wenting Z¹, Yu S¹, Honglin W¹, Tengfei Z¹, Guoyuan W¹, Jiping Z⁴, Chunmao Z³, Meilin J⁵, Yuwei G⁶, Huabin S⁷, Zongzheng Z^8,9.
Author information

1 Institute of Animal Husbandry and Veterinary Sciences, Hubei Academy of Agricultural Sciences, Wuhan, China. 2 Institute of Mountainous Area Research, College of Veterinary Medicine, Hebei Agricultural University, Baoding, 071001, Hebei, China. 3 Institute of Military Veterinary, Academy of Military Medical Sciences, 666 West Liuying Road, Changchun, 130122, Jilin, China. 4 Hubei Engineering Research Center of Viral Vector, Wuhan university of Bioengineering, 430415, Wuhan, China. 5 College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, China. 6 Institute of Military Veterinary, Academy of Military Medical Sciences, 666 West Liuying Road, Changchun, 130122, Jilin, China. gaoyuwei@gmail.com. 7 Institute of Animal Husbandry and Veterinary Sciences, Hubei Academy of Agricultural Sciences, Wuhan, China. shhb1961@163.com. 8 Institute of Animal Husbandry and Veterinary Sciences, Hubei Academy of Agricultural Sciences, Wuhan, China. 329517286@qq.com. 9 Institute of Military Veterinary, Academy of Military Medical Sciences, 666 West Liuying Road, Changchun, 130122, Jilin, China. 329517286@qq.com.

Abstract

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 α 2,3 and α 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 a Y280-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 588 V 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.


PMID: 31875046 DOI: 10.1038/s41598-019-56122-6
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