2. Academic Validation
  3. Porcine reproductive and respiratory syndrome virus regulates lipid droplet accumulation in lipid metabolic pathways to promote viral replication

Porcine reproductive and respiratory syndrome virus regulates lipid droplet accumulation in lipid metabolic pathways to promote viral replication

  • Virus Res. 2023 Jun 7;333:199139. doi: 10.1016/j.virusres.2023.199139.
Yunlong Yang 1,  Yizhuo Luo 1,  Songqiang Yi 2,  Qi Gao 1,  Ting Gong 3,  Yongzhi Feng 4,  Dongdong Wu 3,  Xiaoyu Zheng 3,  Heng Wang 1,  Guihong Zhang 5,  Yankuo Sun 6
Affiliations

Affiliations

  • 1 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.
  • 2 Agricultural Technology Extension Center of Jiangxi Province, Nanchang, China.
  • 3 Guangdong Provincial Key Laboratory of Zoonosis Prevention and Control, College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, PR China; Key Laboratory of Animal Vaccine Development, Ministry of Agriculture and Rural Affairs, PR China.
  • 4 Guangdong Provincial Key Laboratory of Zoonosis Prevention and Control, College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, PR China.
  • 5 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; Key Laboratory of Animal Vaccine Development, Ministry of Agriculture and Rural Affairs, PR China.
  • 6 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; Key Laboratory of Animal Vaccine Development, Ministry of Agriculture and Rural Affairs, PR China. Electronic address: yankuosun@scau.edu.cn.
PMID: 37217033 DOI: 10.1016/j.virusres.2023.199139
Abstract

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.

Keywords

Lipid droplet; Lipid metabolism; Nf-κb signaling pathway; PRRSV.

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