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.

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.

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