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

文献类型： 外文期刊

作者： Zhao, Haiyuan 1 ; Zheng, Dianzhong 2 ; Chang, Qinyuan 1 ; Zhang, Hailin 3 ; Shao, Yilan 1 ; Li, Jiaxuan 1 ; Cui, Wen 1 ; Jiang, Yanping 1 ; Tang, Lijie 1 ; Li, Yijing 1 ; Wang, Xiaona 1 ;

作者机构： 1.Northeast Agr Univ, Coll Vet Med, Harbin 150030, Peoples R China

2.Heilongjiang Acad Agr Sci, Inst Anim Husb, Harbin 150086, Peoples R China

3.Chongqing Acad Anim Sci, Chongqing 402460, Peoples R China

4.Heilongjiang Key Lab Anim Dis Control & Pharmaceut, Harbin 150030, Peoples R China

关键词： PEDV NSP6; IPEC-J2; TLR4; AKT-mTOR; autophagy; replication

期刊名称：VIRUSES-BASEL （ 影响因子：3.5； 五年影响因子：3.7 ）

ISSN：

年卷期： 2024 年 16 卷 11 期

页码：

收录情况： SCI

摘要： 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 cells provided a basis for the in-depth analysis of the pathogenic mechanism of PEDV infection-induced autophagy and promotion of self-replication and also provided an important target for the study of PEDV antiviral drugs. In conclusion, we elucidated that the PEDV infection of IPEC-J2 cells could induce autophagy and found that PEDV could use autophagy to promote its own replication.

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