Yu Zhijun, Sun Weiyang, Zhang Xinghai, Cheng Kaihui, Zhao Chuqi, Xia Xianzhu, Gao Yuwei
Institute of Poultry Science, Shandong Academy of Agricultural Sciences, Jinan, 250023, China.
Key Laboratory of Jilin Province for Zoonosis Prevention and Control, Military Veterinary Research Institute, Academy of Military Medical Sciences, Changchun, 130122, China.
Vet Microbiol. 2017 Aug;207:97-102. doi: 10.1016/j.vetmic.2017.06.009. Epub 2017 Jun 10.
Although H1N2 avian influenza virus (AIV) only infect birds, documented cases of swine infection with H1N2 influenza viruses suggest this subtype AIV may pose a potential threat to mammals. Here, we generated mouse-adapted variants of a H1N2 AIV to identify adaptive changes that increased virulence in mammals. MLD of the variants were reduced >1000-fold compared to the parental virus. Variants displayed enhanced replication in vitro and in vivo, and replicate in extrapulmonary organs. These data show that enhanced replication capacity and expanded tissue tropism may increase the virulence of H1N2 AIV in mice. Sequence analysis revealed multiple amino acid substitutions in the PB2 (L134H, I647L, and D701N), HA (G228S), and M1 (D231N) proteins. These results indicate that H1N2 AIV can rapidly acquire adaptive amino acid substitutions in mammalian hosts, and these amino acid substitutions collaboratively enhance the ability of H1N2 AIV to replicate and cause severe disease in mammals.
尽管H1N2禽流感病毒（AIV）仅感染鸟类，但有记录的猪感染H1N2流感病毒的病例表明，这种AIV亚型可能对哺乳动物构成潜在威胁。在此，我们产生了一种H1N2 AIV的小鼠适应性变体，以确定增加哺乳动物毒力的适应性变化。与亲本病毒相比，变体的半数致死量降低了1000倍以上。变体在体外和体内均表现出增强的复制能力，并能在肺外器官中复制。这些数据表明，增强的复制能力和扩大的组织嗜性可能会增加H1N2 AIV在小鼠中的毒力。序列分析揭示了PB2（L134H、I647L和D701N）、HA（G228S）和M1（D231N）蛋白中的多个氨基酸替换。这些结果表明，H1N2 AIV可在哺乳动物宿主中迅速获得适应性氨基酸替换，并且这些氨基酸替换协同增强了H1N2 AIV在哺乳动物中复制和引起严重疾病的能力。
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