NLRX1 Mediates the Disruption of Intestinal Mucosal Function Caused by Porcine Astrovirus Infection via the Extracellular Regulated Protein Kinases/Myosin Light-Chain Kinase (ERK/MLCK) Pathway

文献类型： 外文期刊

第一作者： Tao, Jie

作者： Tao, Jie;Cheng, Jinghua;Shi, Ying;Li, Benqiang;Tang, Pan;Jiao, Jiajie;Liu, Huili;Tao, Jie;Cheng, Jinghua;Shi, Ying;Li, Benqiang;Tang, Pan;Jiao, Jiajie;Liu, Huili;Tao, Jie;Cheng, Jinghua;Shi, Ying;Li, Benqiang;Tang, Pan;Jiao, Jiajie;Liu, Huili

作者机构：

关键词： porcine astrovirus; NLRX1; mitophagy; ERK/MLCK; intestinal mucosal barrier

期刊名称：CELLS （ 影响因子：5.1； 五年影响因子：6.0 ）

ISSN：

年卷期： 2024 年 13 卷 11 期

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收录情况： SCI

摘要： Porcine astrovirus (PAstV) has a potential zoonotic risk, with a high proportion of co-infection occurring with porcine epidemic diarrhea virus (PEDV) and other diarrheal pathogens. Despite its high prevalence, the cellular mechanism of PAstV pathogenesis is ill-defined. Previous proteomics analyses have revealed that the differentially expressed protein NOD-like receptor X1 (NLRX1) located in the mitochondria participates in several important antiviral signaling pathways in PAstV-4 infection, which are closely related to mitophagy. In this study, we confirmed that PAstV-4 infection significantly up-regulated NLRX1 and mitophagy in Caco-2 cells, while the silencing of NLRX1 or the treatment of mitophagy inhibitor 3-MA inhibited PAstV-4 replication. Additionally, PAstV-4 infection triggered the activation of the extracellular regulated protein kinases/ myosin light-chain kinase (ERK/MLCK) pathway, followed by the down-regulation of tight-junction proteins (occludin and ZO-1) as well as MUC-2 expression. The silencing of NLRX1 or the treatment of 3-MA inhibited myosin light-chain (MLC) phosphorylation and up-regulated occludin and ZO-1 proteins. Treatment of the ERK inhibitor PD98059 also inhibited MLC phosphorylation, while MLCK inhibitor ML-7 mitigated the down-regulation of mucosa-related protein expression induced by PAstV-4 infection. Yet, adding PD98059 or ML-7 did not affect NLRX1 expression. In summary, this study preliminarily explains that NLRX1 plays an important role in the disruption of intestinal mucosal function triggered by PAstV-4 infection via the ERK/MLC pathway. It will be helpful for further antiviral drug target screening and disease therapy.

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