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猪圆环病毒2型ORF5蛋白通过PERK-eIF2α-ATF4和mTOR-ERK1/2-AMPK信号通路诱导自噬以促进PK-15细胞中的病毒复制。

Porcine Circovirus Type 2 ORF5 Protein Induces Autophagy to Promote Viral Replication via the PERK-eIF2α-ATF4 and mTOR-ERK1/2-AMPK Signaling Pathways in PK-15 Cells.

作者信息

Lv Jiangman, Jiang Yanfen, Feng Quanwen, Fan Zhixin, Sun Ying, Xu Panpan, Hou Yufeng, Zhang Xiuping, Fan Yuxin, Xu Xingang, Zhang Yanming, Guo Kangkang

机构信息

College of Veterinary Medicine, Northwest A&F University, Yangling, China.

College of Animal Science, Tarim University, Alar, China.

出版信息

Front Microbiol. 2020 Feb 28;11:320. doi: 10.3389/fmicb.2020.00320. eCollection 2020.

DOI:10.3389/fmicb.2020.00320
PMID:32184774
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7058596/
Abstract

Porcine circovirus type 2 (PCV2) is the primary causative agent that causing porcine circovirus-associated disease (PCVAD). The open reading frame 5 (ORF5) protein is a newly discovered non-structural protein in PCV2, which the function in viral pathogenesis remains unknown. The aim of this study was to investigate the mechanism of PCV2 ORF5 protein on autophagy and viral replication. The pEGFP-tagged ORF5 gene was ectopic expressed in PK-15 cells and an ORF5-deficient PCV2 mutant strain (PCV2) were used to infected PK-15 cells. This study demonstrated that the ORF5 is essential for the of PCV2-induced autophagy. The ORF5 protein triggers the phosphorylation of PERK, eIF2α and the expression of downstream transcription factor ATF4. In addition, ORF5 protein activated the AMPK-ERK1/2-mTOR signaling pathways. These findings suggest that ORF5 play essential roles in the induction of autophagy by PCV2. We further revealed that PCV2 ORF5 promotes viral replication through PERK-eIF2α-ATF4 and AMPK-ERK1/2-mTOR pathways. In conclusion, we showed that PCV2 ORF5 induces autophagy to promote virus replication in PK-15 cells.

摘要

猪圆环病毒2型（PCV2）是引起猪圆环病毒相关疾病（PCVAD）的主要病原体。开放阅读框5（ORF5）蛋白是PCV2中一种新发现的非结构蛋白，其在病毒致病机制中的功能尚不清楚。本研究旨在探讨PCV2 ORF5蛋白对自噬和病毒复制的作用机制。将带有pEGFP标签的ORF5基因在PK-15细胞中异位表达，并使用ORF5缺失的PCV2突变株（PCV2）感染PK-15细胞。本研究表明，ORF5对PCV2诱导的自噬至关重要。ORF5蛋白触发PERK、eIF2α的磷酸化以及下游转录因子ATF4的表达。此外，ORF5蛋白激活了AMPK-ERK1/2-mTOR信号通路。这些发现表明，ORF5在PCV2诱导的自噬中起重要作用。我们进一步揭示，PCV2 ORF5通过PERK-eIF2α-ATF4和AMPK-ERK1/2-mTOR途径促进病毒复制。总之，我们表明PCV2 ORF5诱导自噬以促进PK-15细胞中的病毒复制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4daa/7058596/9c0db200ca76/fmicb-11-00320-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4daa/7058596/af7725219cef/fmicb-11-00320-g001.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4daa/7058596/84e9c789488d/fmicb-11-00320-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4daa/7058596/e4142438ad60/fmicb-11-00320-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4daa/7058596/173ee59da696/fmicb-11-00320-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4daa/7058596/fa961bd7ca8c/fmicb-11-00320-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4daa/7058596/9c0db200ca76/fmicb-11-00320-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4daa/7058596/af7725219cef/fmicb-11-00320-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4daa/7058596/15a7d6d6cfdc/fmicb-11-00320-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4daa/7058596/d21eb18c640c/fmicb-11-00320-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4daa/7058596/033cda56c387/fmicb-11-00320-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4daa/7058596/84e9c789488d/fmicb-11-00320-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4daa/7058596/e4142438ad60/fmicb-11-00320-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4daa/7058596/173ee59da696/fmicb-11-00320-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4daa/7058596/fa961bd7ca8c/fmicb-11-00320-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4daa/7058596/9c0db200ca76/fmicb-11-00320-g009.jpg

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