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Yan, W.* ; Dong, C.* ; Liu, X.* ; Li, H.* ; Peng, J.* ; Jiang, F.* ; Li, H.* ; Stöger, T. ; Wajid, A.* ; Dodovski, A.* ; Mingala, C.N.* ; Andreychuk, D.B.* ; Yin, R.*

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

Vet. Res. 57:24 (2026)
Publ. Version/Full Text DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
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.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Atm–chk2 ; Ddr ; Newcastle Disease Virus ; Cell Cycle Arrest ; Replication; Cell-cycle Arrest; Protein; Kinase; Chk2
ISSN (print) / ISBN 0928-4249
e-ISSN 1297-9716
Quellenangaben Volume: 57, Issue: 1, Pages: , Article Number: 24 Supplement: ,
Publisher BMC
Publishing Place Campus, 4 Crinan St, London N1 9xw, England
Reviewing status Peer reviewed
Grants Natural Science Foundation of Jilin Province
Macedonian- Chinese Scientific and Technological Cooperation project
Shanxi Province Science and Technology Cooperation and Exchange Project