MCL1 promotes porcine epidemic diarrhea virus replication by modulating arachidonic acid metabolic pathway

  • PLoS Pathog. 2026 Apr 24;22(4):e1014170. doi: 10.1371/journal.ppat.1014170.
Hongqi Shang  1  2  3  4 ,  Shanshan Yang  1  2  3  4 ,  Min Sun  1  2  3  4 ,  Yongxiang Zhao  1  2  3  4  5 ,  Rongli Guo  1  2  3  4  5 ,  Wei Wang  1  2  3  4 ,  Bingxu Qian  1  2  3  4 ,  Yunchuan Li  1  2  3  4 ,  Mi Hu  1  2  3  4 ,  Xianyu Bian  1  2  3 ,  Qiuxia Cao  1  2  3 ,  Chengcheng Li  1  2  3 ,  Baochao Fan  1  2  3  4  5  6 ,  Bin Li  1  2  3  4  5  7
Affiliations
  • 1. Institute of Veterinary Medicine, Jiangsu Academy of Agricultural Sciences, Nanjing, China.
  • 2. Key Laboratory of Veterinary Biological Engineering and Technology, Ministry of Agriculture, Nanjing, China.
  • 3. Jiangsu Key Laboratory for Food Quality and Safety-State Key Laboratory Cultivation Base of Ministry of Science and Technology, Nanjing, China.
  • 4. Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou, China.
  • 5. GuoTai (Taizhou) Center of Technology Innovation for Veterinary Biologicals, Taizhou, China.
  • 6. School of Life Sciences, Jiangsu University, Zhenjiang, China.
  • 7. School of Food and Biological Engineering, Jiangsu University, Zhenjiang, China.
PMID: 42030333 DOI: 10.1371/journal.ppat.1014170
Abstract

Porcine epidemic diarrhea virus (PEDV) poses a significant threat to the global swine industry; however, the host factors that support its replication remain poorly understood. Our previous study showed that myeloid cell leukemia 1 (MCL1) is a pro-PEDV replication cellular factor through genome-scale CRISPR-Cas9-knockout (KO) screening. Nevertheless, the molecular mechanism whereby MCL1 promotes PEDV replication is unclear. In this study, we first demonstrated that MCL1 promotes PEDV replication through its Bcl-2 homology (BH) domain. Deletion of MCL1 prevented arachidonic acid (AA) from undergoing β-oxidation which led to the increase of free AA and activation of its secondary metabolic pathways resulting in significant inhibition of PEDV replication. Complementation of MCL1-KO cells with a BH domain fragment of MCL1 restored β-oxidation capacity and rescued PEDV replication. In addition, we identified acyl-CoA synthetase bubblegum family member 1 (ACSBG1) as a novel metabolic regulator that binds to the N-terminus of MCL1, rather than its BH domain, and cooperates with MCL1 to facilitate AA β-oxidation. We further demonstrated that ACSBG1 and MCL1 act together as proviral factors specifically during the replication stage of PEDV Infection. In summary, this work reveals a unique and concerted interaction between MCL1 and ACSBG1 that function together to promote PEDV replication by regulating the AA metabolic pathway.

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