2. Academic Validation
  3. Pseudorabies virus manipulates mitochondrial tryptophanyl-tRNA synthetase 2 for viral replication

Pseudorabies virus manipulates mitochondrial tryptophanyl-tRNA synthetase 2 for viral replication

  • Virol Sin. 2024 Apr 16:S1995-820X(24)00039-7. doi: 10.1016/j.virs.2024.04.003.
Xiu-Qing Li 1,  Meng-Pan Cai 1,  Ming-Yang Wang 1,  Bo-Wen Shi 2,  Guo-Yu Yang 3,  Jiang Wang 4,  Bei-Bei Chu 5,  Sheng-Li Ming 6
Affiliations

Affiliations

  • 1 College of Veterinary Medicine, Henan Agricultural University, Zhengzhou 450046, China; Key Laboratory of Animal Biochemistry and Nutrition, Ministry of Agriculture and Rural Affairs, China; Key Laboratory of Veterinary Biotechnology of Henan Province, Henan Agricultural University, Zhengzhou 450046, China.
  • 2 School of Basic Medicine, Chongqing Medical University, Chongqing 400016, China.
  • 3 Key Laboratory of Animal Biochemistry and Nutrition, Ministry of Agriculture and Rural Affairs, China; Key Laboratory of Veterinary Biotechnology of Henan Province, Henan Agricultural University, Zhengzhou 450046, China; International Joint Research Center of National Animal Immunology, Henan Agricultural University, Zhengzhou 450046, China.
  • 4 College of Veterinary Medicine, Henan Agricultural University, Zhengzhou 450046, China; Key Laboratory of Animal Biochemistry and Nutrition, Ministry of Agriculture and Rural Affairs, China; Key Laboratory of Veterinary Biotechnology of Henan Province, Henan Agricultural University, Zhengzhou 450046, China; Ministry of Education Key Laboratory for Animal Pathogens and Biosafety, Zhengzhou 450046, China. Electronic address: wangjiang@henau.edu.cn.
  • 5 College of Veterinary Medicine, Henan Agricultural University, Zhengzhou 450046, China; Key Laboratory of Animal Biochemistry and Nutrition, Ministry of Agriculture and Rural Affairs, China; Key Laboratory of Veterinary Biotechnology of Henan Province, Henan Agricultural University, Zhengzhou 450046, China; Longhu Advanced Immunization Laboratory, Zhengzhou 450046, China; International Joint Research Center of National Animal Immunology, Henan Agricultural University, Zhengzhou 450046, China; Ministry of Education Key Laboratory for Animal Pathogens and Biosafety, Zhengzhou 450046, China. Electronic address: chubeibei@henau.edu.cn.
  • 6 College of Veterinary Medicine, Henan Agricultural University, Zhengzhou 450046, China; Key Laboratory of Animal Biochemistry and Nutrition, Ministry of Agriculture and Rural Affairs, China; Key Laboratory of Veterinary Biotechnology of Henan Province, Henan Agricultural University, Zhengzhou 450046, China. Electronic address: mingsl911102@163.com.
PMID: 38636706 DOI: 10.1016/j.virs.2024.04.003
Abstract

The pseudorabies virus (PRV) is identified as a double-helical DNA virus responsible for causing Aujeszky's disease, which results in considerable economic impacts globally. The Enzyme tryptophanyl-tRNA synthetase 2 (WARS2), a mitochondrial protein involved in protein synthesis, is recognized for its broad expression and vital role in the translation process. The findings of our study showed an increase in both mRNA and protein levels of WARS2 following PRV Infection in both cell cultures and animal models. Suppressing WARS2 expression via RNA interference in PK-15 cells led to a reduction in PRV Infection rates, whereas enhancing WARS2 expression resulted in increased Infection rates. Furthermore, the activation of WARS2 in response to PRV was found to be reliant on the cGAS/STING/TBK1/IRF3 signaling pathway and the interferon-alpha receptor-1, highlighting its regulation via the type I interferon signaling pathway. Further analysis revealed that reducing WARS2 levels hindered PRV's ability to promote protein and lipid synthesis. Our research provides novel evidence that WARS2 facilitates PRV Infection through its management of protein and lipid levels, presenting new avenues for developing preventative and therapeutic measures against PRV infections.

Keywords

Innate immunity; Lipid synthesis; Protein synthesis; Pseudorabies virus; WARS2.

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