STAT3Tyr705磷酸化在抗流感病毒感染中的作用及其机制

STAT3蛋白具有多种生物学功能，不同病毒感染宿主可导致其活化或抑制，但STAT3在流感病毒感染中的作用及其机制尚不清楚。我们的前期研究发现破坏STAT3 705酪氨酸位点（STAT3 Y705）磷酸化导致宿主抗病毒天然免疫应答显著减弱，故提出假说STAT3 Y705磷酸化介导的STAT3活化在抗流感病毒天然免疫中起重要作用。因此，本项目将系统研究H9N2等流感病毒感染中STAT3活化情况；并使用STAT3显性负突变（STAT3 Y705F）细胞模型和点突变杂合（STAT3 Y705F+/-）小鼠模型，研究STAT3 Y705F突变对流感病毒感染和复制的影响；进而通过转录组测序和蛋白组学技术对感染流感病毒的STAT3 Y705F+/-动物模型进行分析，揭示STAT3 Y705磷酸化在抗流感病毒中的作用机制。这将为阐明流感病毒-宿主互作机制提供新的科学依据，为抗病毒治疗提供潜在的药物靶点。

STAT3 protein has a variety of biological functions and can be activated or inhibited by infections with different viruses in the host. However, the role and its mechanism of STAT3 phosphorylation in influenza virus infection remain unclear. Our previous study found that disruption of phosphorylation of STAT3 705 tyrosine site (STAT3 Y705) significantly attenuated host antiviral innate immune response. Therefore, we hypothesized that activation of STAT3 protein mediated by STAT3 Y705 phosphorylation plays an important role in innate immunity against influenza viruses. Based on this, the project will investigate the activation of STAT3 during the infection of H9N2 and other influenza virus subtypes, and then use STAT3 dominant negative mutant cell (STAT3 Y705F) model and heterozygous mutant mice (STAT3 Y705F+/-) model to study its effect on influenza virus infection and replication. To further reveal the mechanism underlying functional involvement STAT3 Y705, transcriptome sequencing and proteomics techniques were used to analyze STAT3 Y705F+/- animal model infected with influenza virus. Together, these studies will provide scientific foundation for further elucidating the mechanism of influenza virus-host interaction and reveal potential drug targets for antiviral therapy.