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

Qiuyu Zhang¹Feng Yue²Guopeng Sun²Liwei Jiang²Peng Li²Yanping Zhu²Zhike Liu³Yangzhao Zhu²Ruiyan Niu¹Hua He⁴Xuannian Wang^4*Zilong Sun^1*

• ¹Shanxi Agricultural University, Jinzhong, China
• ²Xinxiang University, Xinxiang city, China
• ³Xinyang Agriculture and Forestry University, Xinyang, Henan, China
• ⁴Henan Agricultural University, Zhengzhou, Henan Province, China

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. Here, we found that 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. Overall, 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.