Key Laboratory of Animal Epidemiology of the Ministry of Agriculture, College of Veterinary Medicine, China Agricultural University, Beijing 100193, People's Republic of China.
Key Laboratory of Animal Epidemiology of the Ministry of Agriculture, College of Veterinary Medicine, China Agricultural University, Beijing 100193, People's Republic of China.
Vet Microbiol. 2022 Oct;273:109513. doi: 10.1016/j.vetmic.2022.109513. Epub 2022 Jul 15.
PRRSV and CSFV are both the main pathogens of pigs and pose great threats to the pig industry. Previous studies have shown that PRRSV infection or attenuated virus vaccination can reduce the antibody level of attenuated CSFV vaccine and even cause immune failure. The higher pro-inflammatory cytokines induced by PRRSV might play a significant role in inhibiting the proliferation of CSFV-C. However, the molecular mechanism has not been elucidated yet. Here, the effect of IL-1β, a central mediator of immune-regulating inflammatory responses, on CSFV-C proliferation was investigated, as well as the mechanisms responsible for the production of IL-1β in the PRRSV and CSFV-C co-infection systems. The results showed that co-infection could significantly increase IL-1β production both at mRNA and protein levels with the infection progressing, and the IL-1β upregulation was mainly triggered by PRRSV infection. Additional experiments indicated that IL-1β inhibited the proliferation of CSFV-C in a cell-type independent manner at the replication and release stages. Furthermore, the IL-1β production induced via the TLR4/MyD88 pathway and the downstream signaling pathways NF-κB, ERK1/2, P38, and JNK were involved by treatment with specific inhibitors or siRNA knockdown assays. Finally, we clarified that the NLRP3 inflammasome played a meaningful role in the maturation and release of IL-1β. Together, the accumulated results provided a deeper understanding of the vaccination failure of CSFV caused by PRRSV co-infection as well as targets for the development of novel approaches for the vaccination and control of CSF.
猪繁殖与呼吸综合征病毒（PRRSV）和猪瘟病毒（CSFV）都是猪的主要病原体，对养猪业构成巨大威胁。先前的研究表明，PRRSV 感染或弱毒疫苗接种会降低 CSFV 弱毒疫苗的抗体水平，甚至导致免疫失败。PRRSV 诱导的更高水平促炎细胞因子可能在抑制 CSFV-C 的增殖方面发挥重要作用。然而，其分子机制尚未阐明。在这里，研究了作为免疫调节炎症反应中心介质的白细胞介素-1β（IL-1β）对 CSFV-C 增殖的影响，以及 PRRSV 和 CSFV-C 共感染系统中产生 IL-1β 的机制。结果表明，随着感染的进行，共感染可显著增加 IL-1β 在 mRNA 和蛋白水平上的产生，而 IL-1β 的上调主要是由 PRRSV 感染触发的。此外的实验表明，IL-1β 以细胞类型非依赖的方式在复制和释放阶段抑制 CSFV-C 的增殖。此外，通过使用特定抑制剂或 siRNA 敲低实验，发现 TLR4/MyD88 途径和下游信号通路 NF-κB、ERK1/2、P38 和 JNK 参与了由 IL-1β 诱导的产生。最后，我们阐明了 NLRP3 炎性小体在 IL-1β 的成熟和释放中起重要作用。综上所述，这些结果加深了对 PRRSV 共感染引起的 CSFV 疫苗接种失败的认识，并为开发新型 CSF 疫苗接种和控制方法提供了新的靶点。
