近年出现的H7N9及H10N8 AIV的6个内部基因片段（PB2、PB1、PA、NP、M、NS）都来自于H9N2 AIV（称为H9N2源AIV），我们前期研究表明，与H9N2源AIV在哺乳动物适应性增强相关的位点292V、389K、588V、598M、648V及676M，近年来的比例也明显提高，但627K和701N位点变化不大。更为重要的是PB2 A588V能同时增强H9N2源AIV在禽类及哺乳动物细胞上的聚合酶活性和增殖能力。我们提出假设，“H9N2源AIV PB2蛋白部分位点的进化同时适应禽类和哺乳动物”。拟通过细胞水平和动物水平的实验，确定H9N2源AIV PB2蛋白上能同时提高禽类及哺乳动物适应性的关键位点，利用成熟的病毒-宿主蛋白互作平台，最终解析出关键位点-宿主蛋白的作用机制，为H9N2源AIV的综合防控提供科学数据，为抗流感病毒药物的开发提供新的靶标。

Recently, Human infections with avian influenza H7N9 or H10N8 viruses have been reported in China, while their six internal genes (PB2, PB1, PA, NP, M, NS) are derived from endemic H9N2 influenza viruses circulating in poultry. However, how these viruses adapt to mammalian hosts is unclear. Here we show that besides the commonly recognized viral polymerase subunit PB2 residue 627 K, other residues including 292 V, 389K、588V、598M、648V, and 676 M in PB2 also play critical roles in mammalian adaptation of the H10N8 virus. The avian-origin H10N8 viruse harboring PB2 588V exhibited higher polymerase activity, more efficient replication in mammalian and avian cells when compared to viruses with PB2-588 A. Analyses of available PB2 sequences showed that the proportion of H9N2-origin avian influenza viruses has increased significantly since 2012. Taken together, this project will strongly support the following basic study and disease control.