塞尼卡病毒（SVA）是近年刚发现与猪特发性水疱病（porcine idiopathic vesicular disease，PIVD)相关的新病原，感染猪表现为跛行，水疱并伴有精神沉郁、厌食，新生仔猪病死率高达30%--70%。作为猪新发的传染病病原，SVA感染的致病机制和抗病毒天然免疫仍然是未知的。我们前期研究发现SVA感染或表达3C蛋白均能抑制宿主的I型干扰素应答，但是它们是如何抑制I型干扰素产生的分子机制等尚不清楚。鉴于此，本项目拟开展以下研究：（1）确定SVA 3C蛋白抑制I型干扰素产生信号通路的关键靶点；（2）解析SVA 3C蛋白与靶标蛋白的相互作用及其效应机制；（3）阐明SVA 3C蛋白生物学活性及其生物学意义。本研究为进一步揭示SVA致病机理和免疫逃避的机制奠定基础，为SVA新型疫苗和溶瘤病毒等生物制剂的研发提供理论依据，具有重要意义。

Senecavirus A (SVA), is the single representative species of the genus Senecavirus, family Picornaviridae, has been associated with porcine idiopathic vesicular disease (PIVD) in pigs with lameness and vesicles on the snout and/or coronary bands, sometimes accompanied with lethargy and anorexia. Affected breeding herds had an increase of neonatal mortality (mainly piglets lessen than 7 days) ranging from 30 to 70%. Although SVA was already known as an oncolytic virus of potential use in human therapies, its association with swine disease is novel. As an emerging picornavirus, many aspects of SVA infection pathogenesis and antiviral innate immunity, remain unknown. Our previous studies have demonstrated that SVA infection and overexpression of 3C protein negatively regulate the production of type I interferon, while the molecular mechanism remain elusive. Based on the above findings, further studies will conducted to address the following questions: (1) Determine the signaling molecules targeted by SVA 3C protein in type I interferon pathway; (2) Illuminate the key cleavage sites and biological effects of special signaling molecules targeted by SVA 3C protein; (3) Elucidate the biological activity and biological significance of SVA 3C protein during the course of negatively regulation type I IFN production. Completion of this project will be useful to provide new insights into the pathogenesis and immune evasion mechanism of SVA, and help to provide a theoretical basis for the research and development ofbiological agents such as novel vaccine and oncolytic virus against SVA.