2. Academic Validation
  3. Porcine reproductive and respiratory syndrome virus activates lipid synthesis through a ROS-dependent AKT/PCK1/INSIG/SREBPs axis

Porcine reproductive and respiratory syndrome virus activates lipid synthesis through a ROS-dependent AKT/PCK1/INSIG/SREBPs axis

  • Int J Biol Macromol. 2024 Oct 19;282(Pt 1):136720. doi: 10.1016/j.ijbiomac.2024.136720.
Ying-Xian Ma 1,  Ya-Qi Han 1,  Pei-Zhu Wang 1,  Ming-Yang Wang 1,  Guo-Yu Yang 2,  Jian-Li Li 3,  Jiang Wang 4,  Bei-Bei Chu 5
Affiliations

Affiliations

  • 1 College of Veterinary Medicine, Henan Agricultural University, Zhengzhou 450046, Henan Province, China; Key Laboratory of Animal Biochemistry and Nutrition, Ministry of Agriculture and Rural Affairs, Zhengzhou 450046, Henan Province, China; Key Laboratory of Veterinary Biotechnology of Henan Province, Henan Agricultural University, Zhengzhou 450046, Henan Province, China.
  • 2 Key Laboratory of Animal Biochemistry and Nutrition, Ministry of Agriculture and Rural Affairs, Zhengzhou 450046, Henan Province, China; Key Laboratory of Veterinary Biotechnology of Henan Province, Henan Agricultural University, Zhengzhou 450046, Henan Province, China.
  • 3 College of Veterinary Medicine, Henan Agricultural University, Zhengzhou 450046, Henan Province, China. Electronic address: ljl0613481@henau.edu.cn.
  • 4 College of Veterinary Medicine, Henan Agricultural University, Zhengzhou 450046, Henan Province, China; Key Laboratory of Animal Biochemistry and Nutrition, Ministry of Agriculture and Rural Affairs, Zhengzhou 450046, Henan Province, China; Key Laboratory of Veterinary Biotechnology of Henan Province, Henan Agricultural University, Zhengzhou 450046, Henan Province, China; Ministry of Education Key Laboratory for Animal Pathogens and Biosafety, Zhengzhou 450046, Henan Province, China. Electronic address: wangjiang@henau.edu.cn.
  • 5 College of Veterinary Medicine, Henan Agricultural University, Zhengzhou 450046, Henan Province, China; Key Laboratory of Animal Biochemistry and Nutrition, Ministry of Agriculture and Rural Affairs, Zhengzhou 450046, Henan Province, China; Key Laboratory of Veterinary Biotechnology of Henan Province, Henan Agricultural University, Zhengzhou 450046, Henan Province, China; Longhu Advanced Immunization Laboratory, Zhengzhou 450046, Henan Province, China; International Joint Research Center of National Animal Immunology, Henan Agricultural University, Zhengzhou 450046, Henan Province, China; Ministry of Education Key Laboratory for Animal Pathogens and Biosafety, Zhengzhou 450046, Henan Province, China. Electronic address: chubeibei@henau.edu.cn.
PMID: 39433189 DOI: 10.1016/j.ijbiomac.2024.136720
Abstract

The porcine reproductive and respiratory syndrome virus (PRRSV) is a highly contagious pathogen in pigs. This study aimed to investigate the impact of PRRSV Infection on cellular metabolism, particularly focusing on lipid metabolism to understand its role in promoting viral replication. We conducted a metabolic analysis on MARC-145 cells before and after PRRSV Infection. Our results demonstrated that the most significant alterations in cellular metabolism, accounting for 40.8 % of total changes, were related to lipid metabolism. These changes were primarily driven by the activation of sterol regulatory-element binding proteins (SREBPs), critical regulators of lipid biosynthesis. To understand the mechanisms behind SREBPs activation by PRRSV, we investigated the involvement of upstream effectors, specifically protein kinase B (Akt) and phosphoenolpyruvate carboxykinase 1 (PCK1). Our findings indicated that PRRSV Infection triggered Akt activation, leading to the subsequent activation of PCK1. Activated PCK1 then phosphorylated insulin-induced genes (INSIGs), resulting in their degradation. This degradation facilitated the translocation of SREBPs from the endoplasmic reticulum to the nucleus. Additionally, we observed that PRRSV Infection stimulated the production of Reactive Oxygen Species (ROS), which played a critical role in activating Akt. Collectively, our findings demonstrate that PRRSV enhances lipid synthesis through a ROS-dependent Akt/PCK1/INSIG/SREBPs signaling axis, which provides new insights into the metabolic strategies employed by PRRSV.

Keywords

AKT; Lipid synthesis; PCK1; PRRSV; ROS; SREBPs.

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