猪RNase L不依赖其核糖核酸酶活性与Nsp4互作抑制PRRSV增殖机制初探

猪繁殖与呼吸综合征（PRRS）目前仍是危害养猪业最严重的传染病之一，探究机体抵抗PRRSV感染机制，能够为研发疫苗和有效药物提供新的思路和方法。我们课题组在探究到猪RNase L通过2-5A/RNase L信号通路被激活发挥其核糖核酸酶活性抑制PRRSV增殖外，首次发现猪RNase L不依赖其核糖核酸酶活性仍能抑制PRRSV增殖。本项目将以筛选到的猪RNase L与PRRSV非结构蛋白Nsp4相互作用为突破口，从猪RNase L抑制PPRSV增殖研究及与PRRSV互作蛋白的筛选验证、猪RNase L与PRRSV Nsp4互作的区段或位点的确定、猪RNase L对PRRSV Nsp4蛋白功能的影响和突变与猪RNase L互作的PRRSV Nsp4蛋白位点的病毒拯救与生物学特性研究4个方面阐述其机制。为机体抵抗PRRSV感染提供重要的理论依据，并为预防和控制PRRSV感染提供新的靶向分子。

Porcine reproductive and respiratory syndrome (PRRS) is still one of the most serious viral diseases in the swine industry. Exploring the anti-PRRSV mechanism could provide new ideas and methods for the development of vaccines and effective drugs. Besides that swine RNase L exert its ribonuclease activity to inhibit the proliferation of PRRSV through 2-5A/RNase L signaling pathway, our group found for the first time that swine RNase L could inhibit PRRSV proliferation independent of its ribonuclease activity. This project will take the interaction between swine RNase L and PRRSV nonstructural protein Nsp4 as a breakthrough to elucidate the mechanism from the four aspects: study of inhibition of PRRSV propagation by swine RNase L and screening and verification PRRSV proteins interacted with RNase L, the determination of the interaction regions or sites between swine RNase L and PRRSV Nsp4, the effect of swine RNase L on PRRSV Nsp4 protein function, virus rescue and biological characteristics of PRRSV Nsp4 protein site mutant virus interacting with swine RNase L. This study will provide an important theoretical basis for host anti-PRRSV activity and provide a new target molecule for the prevention and control of PRRSV infection.