抗病毒天然免疫应答是机体应对病毒感染所启动的防御反应。我们前期的研究结果显示敲低酪氨酸蛋白激酶CSK可以显著抑制病毒感染诱导的I型干扰素及其下游基因转录，并影响I型干扰素表达信号转导中关键分子的磷酸化修饰。进一步的研究表明，CSK与DNA识别受体cGAS和接头蛋白MITA相互作用。根据这些前期结果，我们提出的工作假说是：CSK通过调节cGAS或/和MITA磷酸化参与DNA病毒感染诱导I型干扰素表达的信号转导。本项目将利用细胞生物学、分子生物学和生物化学等手段，从分子、细胞和动物模型层面研究CSK在抗DNA病毒天然免疫信号传导中的功能与分子机制。本项目的研究成果将为病毒感染引起的慢性或突发性疾病治疗提供新的分子靶标。

Antiviral immune response is a kind of protective reaction initiated by viral infection. In our previous unpublished study, we found that knockdown of tyrosine kinase CSK significantly inhibits DNA virus-triggered transcription of Type I interferon and downstream genes, and affects the phosphorylation of MITA, TBK1 and IRF3, which are hallmarks for their activation. CSK interacts with the DNA sensor cGAS and adaptor MITA. Based on these results, we hypothesize that CSK regulates DNA virus-triggered expression of type I IFNs by phosphorylation cGAS or/and MITA. In this project, we will investigate molecular mechanisms responsible for DNA virus-triggered signaling mediated by CSK. This project will provide new candidate targets for the treatment of chronic or paroxysmal diseases caused by viral infection.