TLR4和NSP6相互作用诱导的IPEC-J2自噬促进猪流行性腹泻病毒的复制

IF 3.8 3区 医学 Q2 VIROLOGY
Viruses-Basel Pub Date : 2024-11-17 DOI:10.3390/v16111787
Haiyuan Zhao, Dianzhong Zheng, Qinyuan Chang, Hailin Zhang, Yilan Shao, Jiaxuan Li, Wen Cui, Yanping Jiang, Lijie Tang, Yijing Li, Xiaona Wang
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引用次数: 0

摘要

自噬是细胞对抗细胞内病原体的一种重要反应。然而,一些病毒已经进化出了劫持这一防御过程的机制,为病毒在宿主细胞中的复制提供有利条件。猪流行性腹泻病毒(PEDV)已被证明能改变自噬途径;然而,PEDV 通过哪些受体诱导 IPEC-J2 细胞的自噬、自噬是否有利于 PEDV 复制以及 PEDV 蛋白的哪些功能域主要负责诱导自噬,目前仍是未知数。在这里,我们发现 PEDV 感染通过不同的非耦合分子途径诱导宿主细胞自噬。我们采用 RNA-seq 技术,利用转录组学分析了 PEDV 感染的 IPEC-J2 细胞中细胞内基因的表达模式。结果表明,PEDV 通过细胞病原体受体 TLR4 和 AKT-mTOR 通路触发自噬。自噬体检测证明,PEDV 感染会增加自噬体和轻链 3 (LC3)-II 以及下调 AKT-mTOR 磷酸化。我们的研究发现,病毒蛋白 NSP61-2C (56-151aa) 与 TLR4 结合会引发自噬,并使 AKT-mTOR 通路失活,而这两者都是促进 PEDV 感染的关键。通过筛选和分析,发现 TLR4 是参与 PEDV 诱导自噬的关键基因。NSP6(56-151aa)的关键功能域在IPEC-J2细胞中诱导自噬能力的筛选,为深入分析PEDV感染诱导自噬和促进自我复制的致病机制提供了基础,也为研究PEDV抗病毒药物提供了重要靶点。总之,我们阐明了PEDV感染IPEC-J2细胞可诱导自噬,并发现PEDV可利用自噬促进自身复制。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
IPEC-J2 Autophagy Induced by TLR4 and NSP6 Interactions Facilitate Porcine Epidemic Diarrhea Virus Replication.

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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来源期刊
Viruses-Basel
Viruses-Basel VIROLOGY-
CiteScore
7.30
自引率
12.80%
发文量
2445
审稿时长
1 months
期刊介绍: Viruses (ISSN 1999-4915) is an open access journal which provides an advanced forum for studies of viruses. It publishes reviews, regular research papers, communications, conference reports and short notes. Our aim is to encourage scientists to publish their experimental and theoretical results in as much detail as possible. There is no restriction on the length of the papers. The full experimental details must be provided so that the results can be reproduced. We also encourage the publication of timely reviews and commentaries on topics of interest to the virology community and feature highlights from the virology literature in the ''News and Views'' section. Electronic files or software regarding the full details of the calculation and experimental procedure, if unable to be published in a normal way, can be deposited as supplementary material.
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