死亡相关蛋白6
生物
猪流行性腹泻病毒
STAT蛋白
先天免疫系统
ISG15
STAT1
细胞生物学
下调和上调
信号转导
病毒复制
猪圆环病毒
病毒学
转录因子
核蛋白
病毒
免疫系统
免疫学
车站3
基因
遗传学
泛素
作者
Qin Gao,Chuni Zhang,Xiaohan Xu,Xiaoqi Huang,Dexiang Jia,Ying Shan,Weihuan Fang,Xiaoliang Li,Jie Xu
标识
DOI:10.1016/j.vetmic.2024.110065
摘要
Porcine epidemic diarrhea virus (PEDV) is an enteric coronavirus that causes acute enteric disease in piglets and severely threatens the pig industry all over the world. Death domain-associated protein (DAXX) is a classical chaperone protein involved in multiple biological processes, such as cell apoptosis, transcriptional regulation, DNA damage repair, and host innate immunity. However, whether DAXX functions in the anti-PEDV innate immune responses remains unclear. In this study, we found that PEDV infection upregulated DAXX expression and induced its nucleocytoplasmic translocation in IPEC-J2 cells. Furthermore, we found that DAXX overexpression was inhibitory to PEDV replication, while downregulation of DAXX by RNA interference facilitated PEDV replication. The antiviral activity of DAXX was due to its positive effect on IFN-λ3-STAT1 signaling, as DAXX positively regulated STAT1 activation through their interaction in cytoplasm and enhancing the downstream ISG15 expression. Mutation of tryptophan at 621 to alanine in DAXX increased its abundance in the cytoplasm, leading to the upregulation of STAT1 phosphorylation and ISG15 expression. It indicated that cytoplasmic fraction of DAXX was advantageous for the STAT1-ISG15 signaling axis and PEDV inhibition. In summary, these results show that DAXX inhibits PEDV infection by increasing IFN-λ3-induced STAT1 phosphorylation and the downstream ISG15 expression.
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