# PD-1 induces autophagy via the PI3K/AKT/FoxO1 pathway to promote infectious bursal disease virus replication

## TL;DR

The study shows how PD-1 promotes IBDV replication by inducing autophagy through the PI3K/AKT/FoxO1 pathway in chicken cells.

## Contribution

The novel contribution is identifying PD-1's role in IBDV replication via autophagy and the PI3K/AKT/FoxO1 pathway.

## Key findings

- PD-1 interacts with IBDV's VP2 protein to enhance viral replication in DT-40 cells.
- PD-1 overexpression increases autophagy and IBDV titers, while PD-1 silencing has the opposite effect.
- PD-1 activates FoxO1 via the PI3K/AKT pathway to regulate autophagy and VP2 expression.

## Abstract

Autophagy is an important process in host cell responses to viral replication and spread, including those against infectious bursal disease virus (IBDV). Programmed death-1 (PD-1) is a known immunoinhibitory receptor, and its expression causes immune dysfunction in B lymphocytes, resulting in increased progression of immunosuppressive diseases. However, the role of PD-1 in autophagy during IBDV infection remains unclear.

We investigated the mechanism by which chicken PD-1 regulates autophagy during IBDV infection.

IBDV infection enhanced PD-1 expression in chicken tissues and DT-40 cells. Subsequent interaction analyses revealed that PD-1 interacted only with the viral protein VP2 to enhance the IBDV replication in DT-40 cells. PD-1 overexpression significantly increased IBDV-induced autophagy, whereas silencing of PD-1 had the opposite effect in IBDV-infected DT-40 cells. Furthermore, PD-1 enhanced the activation of FoxO1 via the PI3K/AKT pathway. Finally, we demonstrated that autophagy is critical for role of PD-1 in regulating VP2 protein expression and IBDV titers.

These findings present a novel mechanism wherein PD-1 induces autophagy by activating the PI3K/AKT/FoxO1 pathway to facilitate IBDV replication, providing a new avenue in developing universal vaccine adjuvants for IBDV infection control.