2. Academic Validation
  3. Activation of the ATM-Chk2 DNA damage response pathway by Newcastle disease virus enhances viral replication

Activation of the ATM-Chk2 DNA damage response pathway by Newcastle disease virus enhances viral replication

  • Vet Res. 2026 Jan 30;57(1):24. doi: 10.1186/s13567-025-01691-w.
Weiwen Yan # 1,  Chuanrong Dong # 1,  Xinxin Liu # 1 2,  Hongjin Li # 1,  JiaHuiZi Peng 1,  Feng Jiang 1,  Hongli Li 3,  Tobias Stoeger 4,  Abdul Wajid 5,  Aleksandar Dodovski 6,  Claro N Mingala 7,  Dmitry B Andreychuk 8,  Renfu Yin 9
Affiliations

Affiliations

  • 1 State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Key Laboratory of Zoonosis Research, Ministry of Education, Department of Preventive Veterinary Medicine, College of Veterinary Medicine, Jilin University, Changchun, China.
  • 2 College of Food Science and Engineering, Jilin University, Changchun, China.
  • 3 College of Veterinary Medicine, Shanxi Agricultural University, Taiyuan, China.
  • 4 Member of the German Center for Lung Research (DZL), Institute of Lung Health and Immunity (LHI), Comprehensive Pneumology Center (CPC), Helmholtz Zentrum München, Munich, Germany.
  • 5 Department of Biotechnology, Balochistan University of Information Technology, Engineering and Management Sciences, Quetta, Pakistan.
  • 6 Department for Avian Diseases, Faculty of Veterinary Medicine, Ss. Cyril and Methodius University in Skopje, Lazar Pop Trajkov 5-7, Skopje, Macedonia.
  • 7 Livestock Biotechnology Center, Philippine Carabao Center, Science City of Muñoz, Nueva Ecija, Philippines.
  • 8 Reference Laboratory for Avian Viral Diseases, FGBI "Federal Centre for Animal Health" (FGBI "ARRIAH"), Vladimir, Russia.
  • 9 State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Key Laboratory of Zoonosis Research, Ministry of Education, Department of Preventive Veterinary Medicine, College of Veterinary Medicine, Jilin University, Changchun, China. [email protected].
  • # Contributed equally.
PMID: 41618459 DOI: 10.1186/s13567-025-01691-w
Abstract

Newcastle disease (ND), caused by virulent strains of the Newcastle disease virus (NDV), is a highly contagious disease that poses significant economic burdens on the global poultry industry. The DNA damage response (DDR) is a critical cellular mechanism that detects and repairs genomic damage to maintain cellular integrity. While viral infections are known to modulate DDR pathways to either inhibit or enhance viral replication, the interaction between NDV and host DDR remains largely underexplored. Here, we demonstrate that NDV Infection induces significant DNA damage in DF-1 cells and activates DDR signaling, primarily via the ataxia-telangiectasia mutated (ATM) kinase pathway, in a manner dependent on active viral replication. Pharmacological inhibition of ATM kinase, but not ataxia telangiectasia and Rad3-related (ATR) kinase, significantly suppresses NDV replication, alleviates virus-induced G1-phase cell cycle arrest, and modulates the host immune response. Moreover, short interfering RNA (siRNA)-mediated knockdown of Chk2 markedly reduced viral M gene expression and progeny production, indicating that Chk2 is required for efficient NDV replication. These findings suggest that NDV exploits the ATM-Chk2 DDR pathway to establish a replication-favorable environment. Our study provides new insights into NDV pathogenesis and highlights potential targets for Antiviral interventions.

Keywords

ATM–Chk2; DDR; Newcastle disease virus; cell cycle arrest; replication.

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