Ursodeoxycholic acid against TGEV infection via the JAK-STAT1 signaling pathway

IF 2.8 2区农林科学 Q3 MICROBIOLOGY

Veterinary microbiology Pub Date : 2026-05-01 Epub Date: 2026-03-05 DOI:10.1016/j.vetmic.2026.110973

Zhiwei Sun , Aobo Liu , Yi Zhong , Ziyan Song, Guisong Liao, Yi Li, Yanwen Song, Qingyang Li, Xingcui Zhang , Zhenhui Song

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引用次数: 0

Abstract

Transmissible gastroenteritis virus (TGEV) causes transmissible gastroenteritis (TGE), leading to severe diarrhea, vomiting, and dehydration in pigs. Mortality rates among newborn piglets are particularly alarming, causing significant economic losses to the livestock industry. In the absence of effective antiviral drugs, developing novel antiviral agents is crucial. Ursodeoxycholic acid (UDCA), as a hydrophilic endogenous bile acid, plays a key role in regulating bile acid metabolism and treating hepatobiliary diseases. Studies indicate that UDCA exhibits specific antiviral effects against the novel coronavirus. Through validation using Western Blot, qPCR, and IFA techniques, we found that UDCA significantly downregulated TGEV N gene copy number, protein levels, viral load, and nuclear translocation in IPEC-J2 cells. Negative staining electron microscopy revealed that UDCA disrupted the structural integrity of TGEV viral particles. In vivo experiments confirmed that UDCA effectively alleviated TGEV infection symptoms and improved piglet survival rates. Data indicate that UDCA exhibits potent antiviral activity against the TGEV Miller strain. Transcriptomic analysis and validation elucidated its mechanism of action: UDCA significantly activates the TLR3-IRF3 signaling axis, induces IFN-λ3 secretion, activates the JAK-STAT1 pathway, and upregulates transcription of downstream interferon-stimulated genes (ISGs). These synergistic effects collectively establish a defense barrier against TGEV invasion and exert antiviral efficacy.

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熊去氧胆酸通过JAK-STAT1信号通路抗TGEV感染

传染性胃肠炎病毒（TGEV）引起传染性胃肠炎（TGE），导致猪严重腹泻、呕吐和脱水。新生仔猪的死亡率尤其惊人，给畜牧业造成重大经济损失。在缺乏有效抗病毒药物的情况下，开发新型抗病毒药物至关重要。熊去氧胆酸（Ursodeoxycholic acid， UDCA）是一种亲水内源性胆汁酸，在调节胆汁酸代谢和治疗肝胆疾病中起着关键作用。研究表明，UDCA对新型冠状病毒具有特异性抗病毒作用。通过Western Blot、qPCR和IFA技术验证，我们发现UDCA显著下调IPEC-J2细胞中TGEV N基因拷贝数、蛋白水平、病毒载量和核易位。电镜阴性染色显示UDCA破坏了TGEV病毒颗粒的结构完整性。体内实验证实，UDCA能有效缓解TGEV感染症状，提高仔猪存活率。数据表明，UDCA对TGEV Miller株表现出有效的抗病毒活性。转录组学分析和验证阐明了其作用机制：UDCA显著激活TLR3-IRF3信号轴，诱导IFN-λ3分泌，激活JAK-STAT1通路，上调下游干扰素刺激基因（ISGs）的转录。这些协同作用共同建立了抵抗TGEV入侵的防御屏障，并发挥抗病毒作用。

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.