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

## TL;DR

Newcastle disease virus activates a DNA damage response pathway in cells, which helps the virus replicate more effectively.

## Contribution

The study reveals that NDV exploits the ATM–Chk2 pathway to enhance its replication, offering new insights into viral pathogenesis.

## Key findings

- NDV infection induces DNA damage and activates the ATM kinase pathway in DF-1 cells.
- Pharmacological inhibition of ATM kinase suppresses NDV replication and modulates the immune response.
- Knockdown of Chk2 reduces NDV M gene expression and progeny production, showing its necessity for replication.

## 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.