IPEC-J2 Autophagy Induced by TLR4 and NSP6 Interactions Facilitate Porcine Epidemic Diarrhea Virus Replication

作者：Haiyuan Zhao, Dianzhong Zheng, Qinyuan Chang, Hailin Zhang, Yilan Shao, Jiaxuan Li, Cui Wen, Yanping Jiang, Lijie Tang, Yijing Li, Xiaona Wang · 发表于：Viruses · 年份：2024 · DOI：10.3390/v16111787 · 被引用次数：7 · 研究领域：Virus-based gene therapy research、Animal Virus Infections Studies、Autophagy in Disease and Therapy

Autophagy is an important cellular response against intracellular pathogens. However, some viruses have evolved mechanisms to hijack this defensive process to provide favorable conditions for virus replication in host cells. The porcine epidemic diarrhea virus (PEDV) has been shown to alter autophagy pathways; however, it is still unknown through which receptors PEDV induces autophagy in IPEC-J2 cells, whether autophagy facilitates PEDV replication, and which functional domains of PEDV proteins are primarily responsible for inducing autophagy. Here, we found that PEDV infection induces autophagy in host cells via distinct and uncoupled molecular pathways. RNA-seq technology was used to analyze the expression patterns of intracellular genes in PEDV-infected IPEC-J2 cells using transcriptomics. The results demonstrate that PEDV triggers autophagy via the cellular pathogen receptor TLR4 and the AKT-mTOR pathway. As evidenced by autophagosome detection, PEDV infection increases autophagosomes and light chain 3 (LC3)-II as well as downregulated AKT-mTOR phosphorylation. Our study revealed that the binding of the viral protein NSP61-2C (56-151aa) to TLR4 triggers autophagy and inactivates the AKT-mTOR pathway, both of which are critical for facilitating PEDV infection. Through screening and analysis, TLR4 was found to be a key gene involved in PEDV-induced autophagy. The screening of the key functional domains of NSP6 (56-151aa) for their ability to induce autophagy in IPEC-J2 cell...