2. Academic Validation
  3. Phosphorylation of T425 and methylation of R426 synergistically regulate IBDV VP1 function and viral replication

Phosphorylation of T425 and methylation of R426 synergistically regulate IBDV VP1 function and viral replication

  • Vet Microbiol. 2026 Feb:313:110871. doi: 10.1016/j.vetmic.2026.110871.
Huiping Liang 1,  Xiangxiang Gao 2,  Yan Xiao 1,  Rongzhao Sun 3,  Biao Chen 4,  Qinghua Zeng 1,  Zheng Chen 1,  Xiangdong Wu 1,  Huansheng Wu 5
Affiliations

Affiliations

  • 1 Department of Veterinary Preventive Medicine, College of Animal Science and Technology, Jiangxi Agricultural University, Nanchang 330045, PR China; Jiangxi Provincial Key Laboratory for Animal Health, College of Animal Science and Technology, Jiangxi Agricultural University, Nanchang 330045, PR China.
  • 2 China Animal Health and Epidemiology Center, Qingdao 266032, China.
  • 3 Qingdao Lijian Bio-tech Co., Ltd., Qingdao, Shandong 266041, China.
  • 4 Department of Veterinary Preventive Medicine, College of Animal Science and Technology, Jiangxi Agricultural University, Nanchang 330045, PR China; Guangxi Jinling Agriculture and Animal Husbandry Group Co., Ltd., Nanning 530000, China.
  • 5 Department of Veterinary Preventive Medicine, College of Animal Science and Technology, Jiangxi Agricultural University, Nanchang 330045, PR China; Jiangxi Provincial Key Laboratory for Animal Health, College of Animal Science and Technology, Jiangxi Agricultural University, Nanchang 330045, PR China. Electronic address: [email protected].
PMID: 41506171 DOI: 10.1016/j.vetmic.2026.110871
Abstract

Post-translational modifications (PTMs) are essential regulators of viral protein function and replication efficiency. Infectious bursal disease virus (IBDV) polymerase VP1 has been reported to undergo multiple PTMs; however, the interplay among different modifications remains poorly understood. In this study, we identified a novel phosphorylation site at threonine 425 (T425) adjacent to the previously characterized arginine 426 (R426) methylation site of VP1. Mass spectrometry and phospho-specific antibodies confirmed phosphorylation at T425 during IBDV replication. Functional assays demonstrated that phosphorylation at T425 enhances VP1 polymerase activity and promotes viral replication, whereas mutation of this site markedly impaired viral growth. Inhibition experiments further indicated that inhibitor IX significantly inhibit T425 phosphorylation. Importantly, we revealed a synergistic relationship between T425 phosphorylation and PRMT5-mediated R426 methylation, as loss of either modification attenuated the Other. Recombinant IBDV harboring the T425A/R426A double mutation exhibited significantly reduced replication capacity compared to single mutants. Together, our findings uncover a previously unrecognized crosstalk between adjacent phosphorylation and methylation sites in VP1, providing new insights into the fine-tuned regulation of IBDV replication and offering potential targets for Antiviral strategies and vaccine development.

Keywords

IBDV; Methylation of R426; Phosphorylation of T425; Post-translational modifications.

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