2. Academic Validation
  3. Downregulation of the host ribonucleotide reductase subunit M2 via the Wnt/β-catenin pathway is a novel mechanism for duck plague virus replication and a potential antiviral target

Downregulation of the host ribonucleotide reductase subunit M2 via the Wnt/β-catenin pathway is a novel mechanism for duck plague virus replication and a potential antiviral target

  • Poult Sci. 2026 Jun;105(6):106738. doi: 10.1016/j.psj.2026.106738.
Qiqi Yang 1,  Shun Chen 2,  Renyong Jia 2,  Mafeng Liu 2,  Qiao Yang 2,  Bin Tian 2,  Xumin Ou 2,  Zhen Wu 2,  Juan Huang 2,  Di Sun 2,  Dekang Zhu 2,  Xin-Xin Zhao 2,  Shaqiu Zhang 2,  Yu He 2,  Mingshu Wang 3,  Ying Wu 4,  Anchun Cheng 5
Affiliations

Affiliations

  • 1 Research Center of Avian Disease, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, Sichuan 611130, PR China.
  • 2 Research Center of Avian Disease, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, Sichuan 611130, PR China; Engineering Research Center of Southwest Animal Disease Prevention and Control Technology, Ministry of Education of the PR China, Chengdu 611130, China; Agricultural Animal Diseases and Veterinary Public Health Key Laboratory of Sichuan Province, Chengdu 611130, PR China; International Joint Research Center for Animal Disease Prevention and Control of Sichuan Province, Chengdu 611130, PR China.
  • 3 Research Center of Avian Disease, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, Sichuan 611130, PR China; Engineering Research Center of Southwest Animal Disease Prevention and Control Technology, Ministry of Education of the PR China, Chengdu 611130, China; Agricultural Animal Diseases and Veterinary Public Health Key Laboratory of Sichuan Province, Chengdu 611130, PR China; International Joint Research Center for Animal Disease Prevention and Control of Sichuan Province, Chengdu 611130, PR China. Electronic address: [email protected].
  • 4 Research Center of Avian Disease, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, Sichuan 611130, PR China; Engineering Research Center of Southwest Animal Disease Prevention and Control Technology, Ministry of Education of the PR China, Chengdu 611130, China; Agricultural Animal Diseases and Veterinary Public Health Key Laboratory of Sichuan Province, Chengdu 611130, PR China; International Joint Research Center for Animal Disease Prevention and Control of Sichuan Province, Chengdu 611130, PR China. Electronic address: [email protected].
  • 5 Research Center of Avian Disease, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, Sichuan 611130, PR China; Engineering Research Center of Southwest Animal Disease Prevention and Control Technology, Ministry of Education of the PR China, Chengdu 611130, China; Agricultural Animal Diseases and Veterinary Public Health Key Laboratory of Sichuan Province, Chengdu 611130, PR China; International Joint Research Center for Animal Disease Prevention and Control of Sichuan Province, Chengdu 611130, PR China; Institute of Veterinary Medicine and Immunology Drugs, Veterinary Department in College of Animal Science, State Key Laboratory of Green Pesticide, GuiZhou University, GuiYang 550025, PR China. Electronic address: [email protected].
PMID: 41850058 DOI: 10.1016/j.psj.2026.106738
Abstract

Duck plague virus (DPV), a highly contagious alphaherpesvirus, poses a significant threat to the global waterfowl industry. A comprehensive understanding of virus-host interactions is critical for developing effective control strategies. While DPV replication is known to depend on host cellular machinery, the mechanisms by which it manipulates host metabolism to its advantage remain poorly defined. Using RNA-seq analysis of DPV-infected duck embryo fibroblasts (DEFs), we identified a significant downregulation of genes involved in nucleotide metabolism, particularly the ribonucleotide reductase small subunit M2 (RRM2). Both in vitro and in vivo experiments confirmed that DPV Infection markedly reduced RRM2 expression at the mRNA and protein levels. Mechanistically, we demonstrated that DPV suppresses RRM2 expression in a manner dependent on viral DNA replication by activating the Wnt/β-catenin signaling pathway, leading to ubiquitin-mediated degradation of RRM2. Functional studies revealed that RRM2 acts as a host restriction factor against DPV, as its overexpression inhibited viral genome replication and propagation, whereas its knockdown or inhibition with hydroxyurea (HU) promoted viral replication. In conclusion, our study unveils a novel strategy whereby DPV enhances its replication by hijacking the Wnt/β-catenin pathway to degrade the host metabolic enzyme RRM2. These findings not only deepen our understanding of DPV pathogenesis but also identify the Wnt/β-catenin-RRM2 axis as a promising target for developing novel Antiviral interventions against duck plague.

Keywords

Antiviral target; Duck plague virus (DPV); RRM2; Ribonucleotide reductase (RNR); Wnt/β-catenin signaling.

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