猪繁殖与呼吸综合征病毒（PRRSV）通过调控宿主天然免疫应答来实现免疫逃逸，病毒的非结构蛋白在免疫逃逸过程中发挥了关键作用。本项目前期初步研究发现PRRSV非结构蛋白11（nsp11）显著抑制宿主NLRP3炎症小体的激活，caspase-1可能是nsp11作用的关键节点之一，提示nsp11可能通过一种或多种机制调控NLRP3炎症小体的激活，逃逸宿主免疫监视。本研究拟通过免疫共沉淀、慢病毒载体介导的过表达等技术验证nsp11抑制炎症小体激活的功能；通过研究nsp11对炎症小体分子表达及泛素化修饰等方面的影响，明确nsp11抑制炎症小体的关键节点分子；进一步通过IP-MS方法发现新的调控关键节点分子的蛋白，研究nsp11对其调控NLRP3炎症小体的影响，阐明病毒通过nsp11抑制NLRP3炎症小体激活实现免疫逃逸的分子机制，为探索病毒的致病机制及防控提供理论依据。

Nonstructural proteins of porcine reproductive and respiratory syndrome virus (PRRSV) play critical roles in the evasion of host immune system by modulating innate immune responses. Our preliminary studies found that viral nonstructural protein 11 (nsp11) significantly inhibits the activation of NLRP3 inflammasome, and that caspase-1 may be one of key nodes in regulating NLRP3 inflammasome activation, suggesting that nsp11 may regulate the activation of NLRP3 inflammasome via various mechanisms. Therefore, this proposal is aimed to: 1) test the inhibition of NLRP3 inflammasome activation by nsp11 using immunoprecipitation and lentiviral vector-mediated nsp11 overexpression in PAMs and THP-1 cells; 2) investigate the key nodes in regulation of NLRP3 inflammasome by nsp11 using co-immunoprecipitation, GST pulldown, colocalization and nsp11 overexpression , and clarify the key nodes related to the suppression of NLRP3 inflammasome activation by nsp11; 3) identify new molecules involved in PRRSV induced NLRP3 inflammasome, and explore the effect of nsp11 in the regulation of NLRP3 inflammasome activation by the identified molecules, to clarify the molecular mechanism of nsp11 inhibiting NLRP3 inflammasome activation. This project is expected to uncover the molecular mechanisms of PRRSV nsp11 suppressing NLRP3 inflammasome activation, and to provide scientific data for elucidating pathogenic mechanisms of PRRSV.