抗体介导的PRRSV感染通过FcγRI抑制I型干扰素产生的分子机制

PRRSV是引起我国养猪业巨大经济损失的重要病原，其典型致病特征是抗体介导的病毒感染性增强及持续性感染，造成常规疫苗的免疫防控效果不理想。申请人前期研究发现：抗体介导的PRRSV感染可通过FcγRI抑制I型干扰素产生，从而增强病毒复制并促进其持续性感染，但具体机制不明。本项目拟运用免疫共沉淀、蛋白质质谱等鉴定与FcγRI互作的胞内信号抑制分子，探究它们在负向调控I型干扰素信号通路中的作用。在此基础上，运用Western Blot、基因沉默或过表达等进一步解析感染性PRRSV-抗体免疫复合物如何利用FcγRI负向调控I型干扰素信号通路。研究结果通过揭示抗体介导的PRRSV感染通过FcγRI抑制I型干扰素产生的分子机制，有助于阐明该病毒持续性感染的致病机制，为新型PRRS疫苗研制或抗PRRSV药物靶标发掘提供参考。

Porcine reproductive and respiratory syndrome virus (PRRSV) is an important pathogen causing heavy economic losses to the swine industry in China. Because the antibodies specific for PRRSV can enhance PRRSV infection and mediate PRRSV-persistent infection, it is challenging to control PRRSV using traditional vaccine-based immune preventive measures. The applicant's previous studies found that antibody-mediated PRRSV infection inhibited the production of type I interferon (IFN) via Fc gamma receptor I (FcγRI), thereby resulting in enhanced PRRSV infection and contributing to the pathogenesis of PRRSV persistent-infection. However, the precise molecular mechanisms of type I IFN production inhibition were unclear. This project will identify the intracellular signaling suppressor molecules interacting with FcγRI and explore their roles in negatively regulating type I IFN signaling pathways, using coimmunoprecipitation, protein mass spectrometry analysis so on. On this basis, we will further analyze how infectious PRRSV-antibody immune complexes negatively regulate type I IFN signaling pathways by utilizing FcγRI using western blot, gene silencing or overexpression so on. We will reveal the molecular mechanisms of inhibition of type I IFN production by antibody-mediated PRRSV infection through FcγRI. Research results will elucidate the pathogenesis of PRRSV persistent-infection, which will provide references for screening targets of novel PRRS vaccines or antiviral drugs against the PRRSV.