USP8 suppresses porcine reproductive and respiratory syndrome virus replication by positively regulating MAVS mediated Ⅰ-IFN signaling

IF 2.4 2区 农林科学 Q3 MICROBIOLOGY Veterinary microbiology Pub Date : 2024-11-01 DOI:10.1016/j.vetmic.2024.110286
Xiaobo Chang , Zhaopeng Li , Mengqi Wang , Kanglei Pei , Jucai Wang , Jianhe Hu , Ke Ding , Yafei Chang
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Abstract

Porcine reproductive and respiratory syndrome virus (PRRSV) is an important RNA virus that has caused huge economic losses to swine industry in the whole world. Ubiquitin specific protease 8 (USP8), a pivotal regulator of protein degradation, intricately contributes to orchestrating the delicate balance of various biological processes through its deubiquitinating activity. However, the role of USP8 in antiviral immune response to PRRSV remains elusive. In the study, by means of overexpressing USP8, we identified that USP8 suppressed the replication of PRRSV, while reducing USP8 expression using siRNA significantly led to the promotion of PRRSV replication. And USP8 facilitates the production of IFN-β and some IFN-stimulated genes (ISGs) during PRRSV infection. Mechanistically, USP8 promoted mitochondrial antiviral signaling protein (MAVS)-mediated IFN-β signaling. Moreover, USP8 interacted with MAVS and exerted anti-PRRSV effects in a MAVS-dependent manner. This study highlights the importance of USP8 in regulating PRRSV replication, which may enhance our comprehension of its role in innate immunity and its impact on viral replication.
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USP8 通过正向调节 MAVS 介导的 Ⅰ-IFN 信号传导,抑制猪繁殖与呼吸综合征病毒的复制。
猪繁殖与呼吸综合征病毒(PRRSV)是一种重要的 RNA 病毒,给全球养猪业造成了巨大的经济损失。泛素特异性蛋白酶 8(USP8)是蛋白质降解的关键调控因子,通过其去泛素化活性协调各种生物过程的微妙平衡。然而,USP8 在 PRRSV 的抗病毒免疫反应中的作用仍然难以捉摸。在这项研究中,通过过表达 USP8,我们发现 USP8 可抑制 PRRSV 的复制,而使用 siRNA 减少 USP8 的表达则可显著促进 PRRSV 的复制。USP8在PRRSV感染过程中促进IFN-β和一些IFN刺激基因(ISGs)的产生。从机制上讲,USP8 促进了线粒体抗病毒信号蛋白(MAVS)介导的 IFN-β 信号转导。此外,USP8 与 MAVS 相互作用,并以依赖 MAVS 的方式发挥抗 PRRSV 作用。这项研究强调了 USP8 在调控 PRRSV 复制中的重要性,这可能会加深我们对 USP8 在先天性免疫中的作用及其对病毒复制的影响的理解。
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来源期刊
Veterinary microbiology
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.
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