I型干扰素在抗病毒免疫中发挥重要作用。近年来的研究认为cGAS-STING通路是DNA病毒诱导I型干扰素产生的主要通路。我们前期研究发现，PCV2抑制其它DNA病毒诱导的I型干扰素产生，宿主gC1qR和HDAC6及其介导的细胞自噬在PCV2抑制cGAS-STING通路活化过程中发挥重要的调控作用，但作用机制未见报道。本项目拟首先检测PCV2感染对cGAS-STING通路关键信号分子表达、翻译后修饰和活性的影响，筛选出该通路中受gC1qR、HDAC6和自噬调控的靶分子，并明确调控方式；在此基础上鉴定参与该调控过程的gC1qR/HDAC6互作分子、上游信号通路和调控分子，明确gC1qR/HDAC6对这些分子和通路的调控作用与方式、以及这些分子和通路间的关系，绘制PCV2抑制cGAS-STING通路活化的分子作用网络图。研究结果将从干扰素产生水平揭示PCV2感染猪对其它DNA病毒易感的分子机制。

Type I interferons play important roles in the innate immunity against various viruses infection. Recent studies have demonstrated that cGAS-STING pathway play a pivotal role in the process of DNA viruses induction of type I interferon production. Our previous studies have found that PCV2 infection inhibits the production of type I interferon induced by other DNA viruses. Knocking out both gC1qR and HDAC6 can prevent the formation of autolysosomes in PCV2-infected cells and significantly weaken the inhibitory effects of PCV2 on type I interferon induction, whereas deletion of one of them (gC1qR or HDAC6) can not weaken the inhibitory effects of PCV2 on type I interferon induction even though it can prevent the formation of autolysosomes induced by PCV2. These findings indicate that gC1qR/HDAC6 and them mediated cell autophagy synergisticly play pivotal roles in the process of PCV2 inhibiting type I interferon production. This project takes cGAS-STING pathway as our research object, to investigate the influence of PCV2 infection on the expression, post-translational modification and subcellular localization of key signal transducing molecules of cGAS-STING pathway when this pathway are activated by other DNA viruses or DNA stimuli; to screen out the target molecules regulated by gC1qR, HDAC6 and autophagy in cGAS-STING pathway, and clarify the regulation mode by which gC1qR and HDAC6 modulate these target molecules; and to identify the regulatory roles of gC1qR and HDAC6 in mediating the formation of PCV2-induced autolysosomes and the degradation of specific target molecules. On this basis, gC1qR/HDAC6 interacting molecules, upstream signaling pathways and regulators involved in the regulation of the target molecules will be further identified, and the regulatory relationship between these interacting molecules, signaling pathways, regulators and target molecules will be clarified. Taken together, we will eventually map out the molecular action network of PCV2 inhibiting the activation of cGAS-STING pathway and clarify the related molecular signal transduction mechanisms by which gC1qR and HDAC6 inhibit the activation of key target molecules of cGAS-STING pathway in PCV2-infected cells. This study will provide a new insight into understanding the molecular mechanism of susceptibility of PCV2-infected piglets to other DNA viruses at the level of type I interferon production.