Guangdong Provincial Key Laboratory of Zoonosis Prevention and Control, College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, PR China; Maoming Branch, Guangdong Laboratory for Lingnan Modern Agriculture, Maoming 525000, China.
Agricultural Technology Extension Center of Jiangxi Province, Nanchang, China.
Virus Res. 2023 Aug;333:199139. doi: 10.1016/j.virusres.2023.199139. Epub 2023 Jun 7.
Porcine reproductive and respiratory syndrome (PRRS) is a severe respiratory disease caused by porcine reproductive and respiratory syndrome virus (PRRSV) that can lead to the abortion of pregnant sows and decreased boar semen quality. However, the mechanisms of PRRSV replication in the host have not yet been fully elucidated. As lipid metabolism and lipid droplets (LDs) have been reported to play important roles in the replication of various viruses, we aimed to explore the mechanisms through which LDs affect PRRSV replication. Laser confocal and transmission electron microscopy revealed that PRRSV infection promoted intracellular LD accumulation, which was significantly reduced by treatment with the NF-κB signaling pathway inhibitors BAY11-7082 and metformin hydrochloride (MH). In addition, treatment with a DGAT1 inhibitor significantly reduced the protein expression of Phosphorylated NF-ΚB P65and PIκB and the transcription of IL-1β and IL-8 in the NF-κB signaling pathway. Furthermore, we showed that the reduction of the NF-κB signaling pathway and LDs significantly reduced PRRSV replication. Together, the findings of this study suggest a novel mechanism through which PRRSV regulates the NF-κB signaling pathway to increase LD accumulation and promote viral replication. Moreover, we demonstrated that both BAY11-7082 and MH can reduce PRRSV replication by reducing the NF-κB signaling pathway and LD accumulation. This study lays a theoretical foundation for research on the mechanism of PRRS prevention and control, as well as the research and development of antiviral drugs.
猪繁殖与呼吸综合征（PRRS）是一种由猪繁殖与呼吸综合征病毒（PRRSV）引起的严重呼吸道疾病，可导致妊娠母猪流产和公猪精液质量下降。然而，PRRSV 在宿主中的复制机制尚未完全阐明。由于脂质代谢和脂滴（LDs）已被报道在各种病毒的复制中发挥重要作用，我们旨在探索 LDs 影响 PRRSV 复制的机制。激光共聚焦和透射电子显微镜显示，PRRSV 感染促进了细胞内 LD 的积累，而 NF-κB 信号通路抑制剂 BAY11-7082 和盐酸二甲双胍（MH）的处理显著减少了 LD 的积累。此外，DGAT1 抑制剂的处理显著降低了 NF-κB 信号通路中磷酸化 NF-ΚB P65 和 PIκB 的蛋白表达以及 IL-1β 和 IL-8 的转录。此外，我们表明 NF-κB 信号通路和 LD 的减少显著降低了 PRRSV 的复制。综上所述，本研究提出了一种新的机制，即 PRRSV 通过调节 NF-κB 信号通路增加 LD 积累并促进病毒复制。此外，我们证明 BAY11-7082 和 MH 均可通过减少 NF-κB 信号通路和 LD 积累来降低 PRRSV 的复制。本研究为 PRRS 的防控机制以及抗病毒药物的研究与开发奠定了理论基础。
