# Chicken caspase-3 promotes IBDV replication via the cleavage of IRF7

## TL;DR

Chicken caspase-3 helps IBDV replicate by cutting IRF7, a key immune protein, which weakens the host's antiviral defense.

## Contribution

The study reveals a novel immune evasion strategy where IBDV uses Caspase-3 to cleave IRF7, suppressing antiviral responses.

## Key findings

- IBDV activates caspase-3 to promote its replication in chickens.
- Caspase-3 cleaves IRF7, a key activator of antiviral interferon production.
- Blocking Caspase-3 reduces IBDV replication and apoptosis in infected cells.

## Abstract

Infectious bursal disease virus (IBDV) is a highly contagious pathogen that causes severe immunosuppression in chickens, leading to significant economic losses. While apoptosis is a critical host defense mechanism, many viruses exploit it to enhance replication. Here, we demonstrate that IBDV infection induces caspase-dependent apoptosis and that the executioner caspase, Caspase-3, is activated to promote viral replication. Mechanistically, we identify a novel immune evasion strategy: Caspase-3 directly cleaves and degrades interferon regulatory factor 7 (IRF7), a key transcriptional activator of the type I interferon (IFN-β) pathway. This cleavage potently suppresses the host antiviral innate immune response. Furthermore, Caspase-3 activity exacerbates IBDV-induced apoptosis. Consequently, pharmacological inhibition of Caspase-3 significantly reduced viral load and apoptosis, whereas its overexpression produced opposite effects. Our findings reveal that IBDV hijacks the host apoptotic effector Caspase-3 to dismantle the IRF7-mediated antiviral defense, thereby facilitating viral immune evasion and replication. This study provides new insights into viral pathogenesis and suggests Caspase-3/IRF7 as potential therapeutic targets for IBDV control.