DNMT3B inhibits PCV2 replication via targeting TMEM37 to regulate Ca2 + influx in PK15 cells

IF 2.7 2区 农林科学 Q3 MICROBIOLOGY Veterinary microbiology Pub Date : 2025-05-01 Epub Date: 2025-03-16 DOI:10.1016/j.vetmic.2025.110480
Xiaomei Du , Qi Xiao , Li Yang , Yiyi Shan , Yueqing Hu , Wenbin Bao , Shenglong Wu , Zhengchang Wu
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Abstract

Porcine circovirus type 2 (PCV2) is the main pathogen causing postweaning multisystemic wasting syndrome, which leads to enormous losses for porcine industry. However, the regulatory mechanism of PCV2 replication in host cells remains not been clarified. Here, pig DNMT3B was identified as be a host regulator associated with PCV2 infection via RNA-seq analysis. We demonstrated that upregulation of DNMT3B expression can effectively inhibit PCV2 replication in PK15 cells. Besides, TMEM37 acts as a key downstream target of DNMT3B in PCV2-infected PK15 cells. TMEM37 knockdown significantly slowed Ca2+ influx, and thus inhibited PCV2 replication. Taken together, DNMT3B is required for the PCV2-based infection regulation in host cells. Our findings indicated that DNMT3B inhibits PCV2 replication via targeting TMEM37 to regulate Ca2+ influx in PK15 cells, which offering a theoretical foundation for the use of this gene as a key biomarker for breeding strategies seeking to improve porcine disease resistance.
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DNMT3B通过靶向TMEM37调节PK15细胞中的Ca2 +内流来抑制PCV2复制
猪圆环病毒2型(PCV2)是引起断奶后多系统消耗综合征的主要病原体,给养猪业造成巨大损失。然而,PCV2在宿主细胞内复制的调控机制尚不清楚。本研究通过RNA-seq分析,确定猪DNMT3B是与PCV2感染相关的宿主调节因子。我们证明DNMT3B表达上调可以有效抑制PK15细胞中PCV2的复制。此外,在pcv2感染的PK15细胞中,TMEM37作为DNMT3B的关键下游靶点。TMEM37敲低显著减缓Ca2+内流,从而抑制PCV2复制。综上所述,DNMT3B是宿主细胞中基于pcv2的感染调控所必需的。我们的研究结果表明,DNMT3B通过靶向TMEM37来调节PK15细胞中的Ca2+内流来抑制PCV2的复制,这为将该基因作为寻求提高猪疾病抗性的育种策略的关键生物标志物提供了理论基础。
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penicillin-streptomycin
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5-Azacytidine
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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