当前位置: X-MOL 学术Vet. Microbiol. › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
Wnt/β-catenin signaling pathway inhibits porcine reproductive and respiratory syndrome virus replication by enhancing the nuclear factor-κB-dependent innate immune response
Veterinary Microbiology ( IF 2.4 ) Pub Date : 2020-10-23 , DOI: 10.1016/j.vetmic.2020.108904
Jingyu Wang 1 , Lang Gong 2 , Weidong Zhang 3 , Wanli Chen 4 , Haoming Pan 4 , Yuchen Zeng 4 , Xingling Liang 4 , Jun Ma 4 , Guihong Zhang 5 , Heng Wang 1
Affiliation  

The Wnt/β-catenin signaling pathway is an evolutionarily highly conserved signaling pathway related to the replication of various viruses. However, the interaction between the Wnt/β-catenin pathway and porcine reproductive and respiratory syndrome virus (PRRSV) is unknown. In the present study, we showed that PRRSV-infected Marc-145 and PAM cells expressed high levels of c-myc and cyclinD1 mRNA and accumulation of β-catenin in the nucleus. PRRSV nonstructural proteins (Nsps) 1α, 1β, 3, 4, 7, 10, and 12, and proteins encoded by open reading frames (ORFs) 2b, 3, and 5 induced the activation of the Wnt pathway according to TOP/FOP luciferase reporter assay. But, Nsp5 inhibited the activation of the Wnt pathway. Pre-treatment with Wnt3a inhibited PRRSV replication in Marc-145 cells in a dose-dependent manner. Over-expression of β-catenin also inhibited PRRSV replication, while silencing of β-catenin by small hairpin RNA increased its replication in Marc-145 cells. Over-expression of β-catenin increased interferon regulatory factor (IRF)-3 expression and nuclear factor (NF)-κB phosphorylation, NF-κB and interferon-stimulated response element promoter activities, and interferon-β, DExD/H-box helicase 58 (DDX58), interferon-induced protein with tetratricopeptide repeats 1 (IFIT1), interleukin (IL)-1β, tumor necrosis factor (TNF)-α, and IL-8 mRNA expression. Conversely, silencing β-catenin decreased phosphorylated IRF-3 and NF-κB, NF-κB and IFIT1 promoter activities, and IFN-β, DDX58, IFIT1, IL-1β, TNF-α, and IL-8 mRNA levels in Marc-145 cells. Co-immunoprecipitation and immunofluorescence colocalization analyses confirmed that β-catenin interacted with NF-κB in Marc-145 cells. In conclusion, PRRSV infection activates the Wnt/β-catenin signaling pathway via Nsps 1α, 1β, 3, 4, 7, 10, and 12, and proteins encoded by ORFs 2b, 3, and 5. The Wnt/β-catenin pathway then inhibits PRRSV replication by enhancing the NF-κB-dependent innate immune response. These findings further our understanding of the role of the Wnt/β-catenin signaling pathway in regulating PRRSV replication and provide new insights into virus–host interactions.



中文翻译:

Wnt /β-catenin信号通路通过增强依赖核因子-κB的先天免疫应答来抑制猪繁殖与呼吸综合征病毒复制

Wnt /β-catenin信号传导途径是与多种病毒复制相关的进化上高度保守的信号传导途径。然而,Wnt /β-catenin途径与猪繁殖与呼吸综合征病毒(PRRSV)之间的相互作用尚不清楚。在本研究中,我们显示PRRSV感染的Marc-145和PAM细胞在核中表达高水平的c-myc和cyclinD1 mRNA以及β-catenin的积累。PRRSV非结构蛋白(Nsps)1α,1β,3、4、7、10和12,以及由开放阅读框(ORF)2b,3和5编码的蛋白根据TOP / FOP荧光素酶诱导Wnt途径的激活报告基因测定。但是,Nsp5抑制了Wnt途径的激活。用Wnt3a预处理以剂量依赖性方式抑制Marc-145细胞中PRRSV复制。β-catenin的过表达也抑制了PRRSV复制,而通过小发夹RNA沉默β-catenin可以增加其在Marc-145细胞中的复制。β-catenin的过表达增加了干扰素调节因子(IRF)-3的表达和核因子(NF)-κB的磷酸化,NF-κB和干扰素刺激的响应元件启动子的活性,以及​​干扰素-β,DExD / H-box解旋酶的表达58(DDX58),干扰素诱导的四三肽重复序列1(IFIT1),白介素(IL)-1β,肿瘤坏死因子(TNF)-α和IL-8 mRNA表达。相反,沉默β-catenin会降低Marc-的IRF-3和NF-κB,NF-κB和IFIT1启动子活性以及IFN-β,DDX58,IFIT1,IL-1β,TNF-α和IL-8 mRNA水平的磷酸化。 145个细胞。免疫共沉淀和免疫荧光共定位分析证实Marc-145细胞中β-catenin与NF-κB相互作用。总之,PRRSV感染通过Nsps1α,1β,3、4、7、10和12以及由ORF 2b,3和5编码的蛋白激活Wnt /β-catenin信号通路。Wnt /β-catenin途径然后通过增强NF-κB依赖性先天免疫应答来抑制PRRSV复制。这些发现进一步加深了我们对Wnt /β-catenin信号通路在调节PRRSV复制中的作用的理解,并为病毒-宿主相互作用提供了新的见解。然后,Wnt /β-catenin途径通过增强NF-κB依赖性先天免疫应答来抑制PRRSV复制。这些发现进一步加深了我们对Wnt /β-catenin信号通路在调节PRRSV复制中的作用的理解,并为病毒-宿主相互作用提供了新的见解。然后,Wnt /β-catenin途径通过增强NF-κB依赖性先天免疫应答来抑制PRRSV复制。这些发现进一步加深了我们对Wnt /β-catenin信号通路在调节PRRSV复制中的作用的理解,并为病毒-宿主相互作用提供了新的见解。

更新日期:2020-11-12
down
wechat
bug