Hypomethylated interferon regulatory factor 8 recruits activating protein-2α to attenuate porcine epidemic diarrhea virus infection in porcine jejunum

Frontiers in Immunology

Immunology

Zongjun Yin¹  Xianrui Zheng¹  Qiufang Zong²  Wenbin Bao²  Haifei Wang²  Huan Qu²  Shenglong Wu² 

[1] College of Animal Science and Technology, Anhui Agricultural University, Hefei, Anhui, China;College of Animal Science and Technology, Yangzhou University, Yangzhou, Jiangsu, China;

关键词: PEDV;    IRF8;    DNA methylation;    AP-2α;    oxidative stress;    apoptosis;   

DOI  :  10.3389/fimmu.2023.1187144

 received in 2023-03-15, accepted in 2023-07-12,  发布年份 2023

来源: Frontiers

【 摘 要 】

Interferon regulatory factor 8 (IRF8) is a key regulator of innate immune receptor signaling that resists pathogen invasion by regulating cell growth and differentiation. Porcine epidemic diarrhea virus (PEDV) targets the intestine and damages the mucosal barrier. However, whether IRF8 regulates PEDV replication remains unclear. We revealed that PEDV infection activated IRF8 expression. Moreover, IRF8 deletion drastically promoted PEDV replication and invasion, increasing the virus copies and titers. Hypomethylation enrichment of activating protein (AP)-2α was significantly negatively correlated with high IRF8 expression, and AP-2α directly targeted the IRF8 promoter to regulate PEDV replication. Furthermore, IRF8 overexpression decreased the cellular reactive oxygen species levels and mitochondrial membrane potential and increased the antioxidant enzyme activities to alleviate PEDV-induced oxidative damage. IRF8 overexpression suppressed apoptotic gene expression, thereby inhibiting apoptosis in response to PEDV stimulation. Taken together, this study demonstrates that AP-2α is involved in PEDV-induced epigenetic modification of IRF8 to reduce cell apoptosis and oxidative stress and facilitate host resistance to PEDV in the intestinal epithelium.

【 授权许可】

Unknown   
Copyright © 2023 Zong, Qu, Zheng, Wang, Wu, Yin and Bao