Porcine reproductive and respiratory syndrome virus (PRRSV) is a causative pathogen of PRRS that has generated a serious adverse impact on current global pork production. PRRSV primarily infects pig alveolar macrophages, but poor induction of innate immunity after infection often leads to more severe complications. Defining the functional role of each PRRSV non structural protein (NSP) within host cells might be helpful in understanding how PRRSV induces poor innate immunity in host cells. NSP1 of PRRSV exhibits papain like cysteine protease activity and may therefore modulate host cell signaling by degrading a target protein in host cells during infection. In this study, we demonstrated that NSP1 of PRRSV-2 indirectly blocked extracellular signal-regulated kinase (ERK) signaling in polyriboinosinic polyribocytidylic acid (Poly I:C) stimulated pig macrophages (3D4/31 cells). ERK which belongs to the mitogen-activated protein kinase family mediates many biological processes including inflammatory responses during viral infection. The blocking of ERK signaling by NSP1 of PRRSV-2 further leads to the transcriptional inhibition of inflammatory enhancers, cellular communication network factor 1 and 2 (ccn1 and ccn2) through down-regulation of v-fos FBJ murine osteosarcoma viral oncogene homolog (fos) and fosb, the component of activating protein-1 (AP-1) which is an ERK downstream transcription factor. Therefore, NSP1 of PRRSV-2 inhibited the mRNA transcription of ccn1 and ccn2 by blocking the ERK-AP-1 axis in Poly I:C stimulated pig macrophages. These results provide additional evidence supporting that NSP1 has anti-inflammatory function during PRRSV-2 infection.

猪繁殖与呼吸综合症病毒（PRRSV）是PRRS的病原体，已对当前的全球猪肉生产产生了严重的不利影响。PRRSV主要感染猪肺泡巨噬细胞，但感染后先天免疫诱导不良通常会导致更严重的并发症。定义宿主细胞内每个PRRSV非结构蛋白（NSP）的功能作用可能有助于理解PRRSV如何诱导宿主细胞的先天免疫力低下。PRRSV的NSP1表现出类似木瓜蛋白酶的半胱氨酸蛋白酶活性，因此可能在感染过程中通过降解宿主细胞中的靶蛋白来调节宿主细胞信号传导。在这项研究中，我们证明了PRRSV-2的NSP1间接阻断了多核糖核酸聚核糖酸（Poly I：）中的细胞外信号调节激酶（ERK）信号传导。C）刺激的猪巨噬细胞（3D4 / 31细胞）。属于丝裂原活化蛋白激酶家族的ERK介导许多生物学过程，包括病毒感染期间的炎症反应。PRRSV-2的NSP1对ERK信号的阻断进一步导致炎症增强子，细胞通讯网络因子1和2（ccn1和ccn2）通过下调v-fos FBJ鼠骨肉瘤病毒癌基因同源物（fos）和fosb的表达，fosb是活化蛋白1（AP-1）的组成部分，它是ERK下游转录因子。因此，PRRSV-2的NSP1通过阻断Poly I：C刺激的猪巨噬细胞中的ERK-AP-1轴来抑制ccn1和ccn2的mRNA转录。这些结果提供了其他证据，证明NSP1在PRRSV-2感染期间具有抗炎功能。