猪FcγIIb抑制性信号在PRRSV免疫逃避中的作用研究

Porcine reproductive and respiratory syndrome (PRRS) is an economically significant viral disease of swine worldwide, which is caused by porcine reproductive and respiratory syndrome virus (PRRSV). One of important immunological characteristics of PRRSV infection is Antibody-dependent enhancement (ADE). Previously studies have shown that Fcγ receptor (FcγR)-mediated entry of infectious PRRSV immune complexes into macrophages plays a pivotal role in the pathogenesis of the disease. And the porcine FcγRIIb is a key molecule mediating ADE of PRRSV infection. PRRSV was able to suppress the transcription of key antiviral genes TNF-α and IFN-β, when infection was via the ADE pathway. However, the negative regulation of the antiviral response by inhibitory signaling of poFcγRIIb during the PRRSV ADE infection, and the relationship between PRRSV ADE infection alters the innate intracellular immune responses and immune evasion remains obscure. In this study, to elucidate the molecular mechanisms by inhibitory signaling transduction in poFcγRIIb mediating PRRSV immune evasion, we evaluated the negative regulation of the antiviral response by inhibitory signaling of poFcγRIIb during the PRRSV ADE infection. The results will provide a prerequisite theoretical basis for better controlling and prevention of the disease.

猪繁殖与呼吸综合征(PRRS)是由猪繁殖与呼吸综合征病毒(PRRSV)引起的严重危害养猪业的一种病毒性传染病。PRRSV感染可以通过抗体依赖增强作用(ADE)逃避宿主的体液免疫清除作用，这是导致PRRS难以防控的重要原因之一。前期研究结果表明，PRRSV通过IgG Fc受体(FcγR)介导进入巨噬细胞是其重要的致病机制，猪抑制型FcγR(FcγRIIb)可以介导PRRSV的ADE作用，PRRSV ADE感染PAM后可以抑制TNF-α、IFN-β等抗病毒分子的转录。然而，PRRSV是否通过ADE感染激活猪FcγRIIb的下游信号，负调控宿主抗病毒细胞因子，抑制宿主的抗病毒免疫效应，导致免疫逃避，仍不是十分清楚。本课题拟通过研究PRRSV ADE感染过程中猪FcγRIIb抑制信号对宿主抗病毒反应的负调控机制，揭示猪FcγRIIb抑制信号在PRRSV免疫逃避中的作用，为PRRS防控提供理论依据。

猪繁殖与呼吸综合征是由猪繁殖与呼吸综合征病毒引起的严重危害养猪业的一种病毒性传染病。PRRSV感染通过抗体依赖性增强作用（ADE）逃避免疫清除是其重要免疫学特征之一。前期研究结果表明，猪FcγRIIb可以介导PRRSV的ADE作用。FcγRIIb是目前发现的唯一的抑制性受体。然而，FcγRIIb胞内的抑制性信号在PRRSV ADE感染中的作用目前尚不清楚。本课题从FcγRIIb介导的胞内信号转导通路出发，研究猪FcγRIIb胞内保守序列及其介导的信号转导在PRRSV ADE感染中的作用，以及PRRSV ADE感染过程中poFcγRIIb抑制信号对宿主抗病毒反应的负调控作用，从而揭示猪FcγRIIb抑制信号在PRRSV ADE感染中的作用，为进一步研究新型疫苗、开发新型免疫佐剂提供理论依据，为研究FcγR介导ADE作用的具体机制提供新的思路。