The ubiquitin-proteasome system is essential for efficient propagation of Pseudorabies virus

IF 2.4 2区农林科学 Q3 MICROBIOLOGY

Veterinary microbiology Pub Date : 2025-06-13 DOI:10.1016/j.vetmic.2025.110602

Wei Wen , Yi Lu , Zhendong Zhang , Wenqiang Wang , Zhenbang Zhu , Xiangdong Li

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Abstract

Pseudorabies virus (PRV) is a pathogen that affects multiple animal species and can infect nearly all mammals, with pigs being its natural host. PRV infection in pigs causes significant economic losses in global pig industry. The ubiquitin-proteasome system (UPS) plays a crucial role in cellular protein homeostasis by regulating protein quality. Nevertheless, the interplay between PRV and UPS is not well understood. In this study, We investigated the role of UPS in PRV replication. We found that the proteasome inhibitors (MG132, Lactacystin, and Bortezomib) significantly decreased PRV replication in a dose dependent manner. The suppression of the UPS primarily occurs at the early stage of virus replication. MG132 impaired the PRV uncoating process. In addition, PRV infection dramatically reduced the expression of poly-ubiquitin and free ubiquitin. Ectopic expression of ubiquitin in MG132-treated cells partially mitigated the inhibitory effect of MG132 on PRV proliferation. These findings suggest that PRV exploits the UPS to enhance its own replication.

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泛素-蛋白酶体系统对伪狂犬病毒的高效繁殖至关重要

伪狂犬病毒（PRV）是一种影响多种动物物种的病原体，可以感染几乎所有哺乳动物，猪是其天然宿主。猪的PRV感染给全球养猪业造成重大经济损失。泛素-蛋白酶体系统（UPS）通过调节蛋白质质量在细胞蛋白稳态中起着至关重要的作用。然而，PRV和UPS之间的相互作用还不是很清楚。在这项研究中，我们研究了UPS在PRV复制中的作用。我们发现蛋白酶体抑制剂（MG132， Lactacystin和Bortezomib）以剂量依赖的方式显著降低PRV复制。UPS的抑制主要发生在病毒复制的早期阶段。MG132破坏了PRV脱涂层过程。此外，PRV感染显著降低了多泛素和游离泛素的表达。在MG132处理的细胞中，泛素的异位表达部分减轻了MG132对PRV增殖的抑制作用。这些发现表明，PRV利用UPS来增强自身的复制。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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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.