Cyclophilin A promotes porcine deltacoronavirus replication by regulating autophagy via the Ras/AKT/NF-κB pathway

IF 2.4 2区农林科学 Q3 MICROBIOLOGY

Veterinary microbiology Pub Date : 2024-07-22 DOI:10.1016/j.vetmic.2024.110190

Yousheng Peng , Chenchen Li , Liping Zhang , Ruiming Yu , Yonglu Wang , Li Pan , Huichen Guo , Yanming Wei , Xinsheng Liu

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Abstract

Porcine deltacoronavirus (PDCoV) is an important enteric coronavirus that has caused major worldwide economic losses in the pig industry. Previous studies have shown that cyclophilin A (CypA), a key player in aetiological agent infection, is involved in regulating viral infection. However, the role of CypA during PDCoV replication remains unknown. Therefore, in this study, the role of CypA in PDCoV replication was determined. The results demonstrated that PDCoV infection increased CypA expression in LLC-PK1 cells. CypA overexpression substantially promoted PDCoV replication. Proteomic analysis was subsequently used to assess changes in total protein expression levels after CypA overexpression. Gene Ontology (GO) functional analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were used to further determine the mechanisms by which CypA affects viral replication. Proteomic analysis revealed that CypA protein overexpression significantly upregulated 75 differentially expressed proteins and significantly downregulated 172 differentially expressed proteins. The differentially expressed proteins were involved mainly in autophagy and activation of the host innate immune pathway. Subsequent experimental results revealed that the CypA protein promoted viral replication by reducing the levels of natural immune cytokines and mitigated the inhibitory effect of chloroquine (CQ) on viral replication. Further investigation revealed that CypA could activate the Ras/AKT/NF-κB pathway, mediate autophagy signalling and promote PDCoV replication. In summary, the findings of this study may help elucidate the role of CypA in PDCoV replication.

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嗜环蛋白 A 通过 Ras/AKT/NF-κB 途径调节自噬作用，从而促进猪 deltacoronavirus 的复制

猪三角冠状病毒（PDCoV）是一种重要的肠道冠状病毒，给全球养猪业造成了重大经济损失。以往的研究表明，环嗜蛋白 A（CypA）是病原感染的关键角色，参与调控病毒感染。然而，CypA 在 PDCoV 复制过程中的作用仍然未知。因此，本研究确定了 CypA 在 PDCoV 复制过程中的作用。结果表明，PDCoV 感染增加了 LLC-PK1 细胞中 CypA 的表达。CypA的过表达大大促进了PDCoV的复制。随后使用蛋白质组分析评估了CypA过表达后总蛋白表达水平的变化。基因本体（GO）功能分析和京都基因和基因组百科全书（KEGG）通路富集分析被用来进一步确定CypA影响病毒复制的机制。蛋白质组分析表明，CypA 蛋白过表达会显著上调 75 个差异表达蛋白，显著下调 172 个差异表达蛋白。差异表达的蛋白质主要参与自噬和宿主先天免疫途径的激活。随后的实验结果显示，CypA 蛋白通过降低天然免疫细胞因子的水平来促进病毒复制，并减轻氯喹（CQ）对病毒复制的抑制作用。进一步研究发现，CypA 可激活 Ras/AKT/NF-κB 通路，介导自噬信号，促进 PDCoV 复制。总之，本研究的结果可能有助于阐明 CypA 在 PDCoV 复制中的作用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Veterinary microbiology 农林科学-兽医学

CiteScore

5.90

自引率

6.10%

发文量

221

审稿时长

52 days

期刊介绍： Veterinary Microbiology is concerned with microbial (bacterial, fungal, viral) diseases of domesticated vertebrate animals (livestock, companion animals, fur-bearing animals, game, poultry, fish) that supply food, other useful products or companionship. In addition, Microbial diseases of wild animals living in captivity, or as members of the feral fauna will also be considered if the infections are of interest because of their interrelation with humans (zoonoses) and/or domestic animals. Studies of antimicrobial resistance are also included, provided that the results represent a substantial advance in knowledge. Authors are strongly encouraged to read - prior to submission - the Editorials (''Scope or cope'' and ''Scope or cope II'') published previously in the journal. The Editors reserve the right to suggest submission to another journal for those papers which they feel would be more appropriate for consideration by that journal. Original research papers of high quality and novelty on aspects of control, host response, molecular biology, pathogenesis, prevention, and treatment of microbial diseases of animals are published. Papers dealing primarily with immunology, epidemiology, molecular biology and antiviral or microbial agents will only be considered if they demonstrate a clear impact on a disease. Papers focusing solely on diagnostic techniques (such as another PCR protocol or ELISA) will not be published - focus should be on a microorganism and not on a particular technique. Papers only reporting microbial sequences, transcriptomics data, or proteomics data will not be considered unless the results represent a substantial advance in knowledge. Drug trial papers will be considered if they have general application or significance. Papers on the identification of microorganisms will also be considered, but detailed taxonomic studies do not fall within the scope of the journal. Case reports will not be published, unless they have general application or contain novel aspects. Papers of geographically limited interest, which repeat what had been established elsewhere will not be considered. The readership of the journal is global.