Foxp3 inhibits PCV2 replication by reducing the ATPase activity of Rep

IF 2.7 2区 农林科学 Q3 MICROBIOLOGY Veterinary microbiology Pub Date : 2025-02-27 DOI:10.1016/j.vetmic.2025.110441
Ruijiao Jiang , Qiuyan Huang , Ruiting Shen, Yongning Zhang, Lei Zhou, Xinna Ge, Jun Han, Xin Guo, Hanchun Yang
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Abstract

Porcine circovirus type 2 (PCV2) is the pathogen that causes porcine circovirus disease, characterized by severe immunosuppression and significant economic losses in the swine industry. The replicase (Rep), one of the most critical non-structural proteins of PCV2, plays a pivotal role in viral replication. However, the mechanism by which Rep regulates the replication of PCV2 still requires further investigation. Our study demonstrated that PCV2 can infect regulatory T cells (Tregs), and within the nucleus, Rep interacted with Foxp3, while the structural protein capsid protein (Cap) did not exhibit this interaction. Further investigations revealed that the Forkhead domain of Foxp3 was crucial for mediating its interaction with the C-terminal region of Rep, which had an ATPase activity-regulating domain. The interaction between Foxp3 and Rep reduced the ATPase activity of Rep, thereby inhibiting PCV2 replication. This study provided a theoretical foundation for elucidating the role of Rep in PCV2 pathogenesis and contributed to a deeper understanding of the molecular mechanisms underlying PCV2 immune evasion.
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Foxp3通过降低Rep的atp酶活性来抑制PCV2的复制
猪圆环病毒2型(PCV2)是引起猪圆环病毒病的病原体,具有严重的免疫抑制和重大的养猪业经济损失。复制酶(Rep)是PCV2最关键的非结构蛋白之一,在病毒复制过程中起着关键作用。然而,Rep调控PCV2复制的机制仍需进一步研究。我们的研究表明,PCV2可以感染调节性T细胞(Tregs),并且在细胞核内,Rep与Foxp3相互作用,而结构蛋白衣壳蛋白(Cap)不表现出这种相互作用。进一步的研究表明,Foxp3的叉头结构域对于介导其与Rep的c端区域的相互作用至关重要,而Rep具有atp酶活性调节结构域。Foxp3和Rep之间的相互作用降低了Rep的atp酶活性,从而抑制了PCV2的复制。本研究为阐明Rep在PCV2发病机制中的作用提供了理论基础,有助于深入了解PCV2免疫逃避的分子机制。
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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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