禽流感病毒感染人和其他哺乳动物的事件频繁发生，对公共卫生健康构成了严重威胁。已有研究证明，PA基因在禽流感病毒感染哺乳动物方面发挥着重要作用。最近人们发现，由PA基因上核糖体移码产生的PA-X开放阅读框编码一个新的流感蛋白，即PA-X蛋白。PA-X的发现及前期实验结果提示我们，该基因可能影响禽流感病毒对哺乳动物的致病性。本研究拟通过比较具有不同来源和携带不同氨基酸突变PA-X的禽流感病毒在聚合酶活性、细胞感染性以及对哺乳动物模型致病性方面的差异，解析PA-X在禽流感病毒对哺乳动物致病性中的作用，确定PA-X上与致病性相关的关键氨基酸位点，揭示PA-X影响禽流感病毒对哺乳动物致病性的分子机制。研究结果将为人间禽源流感病毒的预警和防控提供理论依据，同时加深人们对PA-X基因功能的认识。

Avian influenza viruses repeatedly infected human and other mammals, posing a significant threat to public health. Previous studies demonstrated that PA gene played an important role in the infection of avian influenza virus for mammals. It was recently found that +1 frameshifting of PA gene resulted in a novel influenza protein called PA-X. The discovery of PA-X and the previous experimental results suggest that this gene might influence the pathogenicity of avian influenza virus in mammals. In this project, we plan to compare the polymerase activity, infectivity in cells, and pathogenicity in mammalian animal model of avian influenza viruses whose PA genes are from different origin or with different mutations. Based on these experiments, we will analyze the effect of PA-X gene on the pathogenicity of avian influenza virus to mammals, determine the crucial amino acid sites in the PA-X gene related to pathogenicity, and reveal the molecular mechanism of the effect of PA-X on the pathogenicity of avian influenza virus in mammals. These results will provide the theoretical foundation for the prewarning, prevention and control of avian-original influenza virus in humans and help the reorganization of the function of PA-X gene.