Curcumin activates the JAK-STAT signaling pathway to enhance the innate immune response against porcine epidemic diarrhea virus infection in vivo and in vitro

IF 2.4 2区 农林科学 Q3 MICROBIOLOGY
Qiancheng Jiang , Xiangyang Liu , Jianbo Yuan , Shujuan Zhang , Yiling Zhang , Zifei Kan , Zheng Niu , Li Zhang , Xia Hu , Yang Zhou , Jing Wang , Fei Li , Lijing Cao , Xingcui Zhang , Chenghong Lei , Zhenhui Song
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Abstract

Porcine epidemic diarrhea (PED) is a highly pathogenic infectious disease caused by porcine epidemic diarrhea virus (PEDV), which has caused significant economic losses to the global pig industry. Due to the high mutability of the PEDV genome, the development of effective vaccines or drugs to prevent and control PEDV is still facing great difficulties. In this study, we found that the natural compound curcumin showed effective antiviral activity against PEDV in VERO-E6 and IPEC-J2 cells. The Janus Kinase-Signal Transducer and Activator of Transcription (JAK-STAT) signaling pathway was screened by transcriptomics as a potential innate immune mechanism of IPEC-J2 cells against PEDV infection. For PEDV, a highly pathogenic virus, cellular autoimmune response is not sufficient to fight against its infection. Our results demonstrated that curcumin could exert antiviral effects by enhancing the JAK-STAT cascade reaction mediated by type I interferon IFN-α and IFN-β in IPEC-J2 cells. In vivo experiments further confirmed the protective effect of curcumin on PEDV-infected piglets and its positive regulation of the JAK-STAT signaling pathway. In vivo, curcumin prophylaxis significantly enhanced IFN-α and IFN-β-induced JAK-STAT signaling and the production of interferon-stimulated genes (ISGs), and increased the innate immune response, thus exerting antiviral effects effectively. In conclusion, our data indicate that curcumin can effectively resist PEDV infection in IPEC-J2 cells and piglets, which provides a new reference for the development of anti-PEDV drugs with important application prospects.
姜黄素激活JAK-STAT信号通路,增强猪流行性腹泻病毒感染的体内外先天免疫应答
猪流行性腹泻(PED)是由猪流行性腹泻病毒(PEDV)引起的一种高致病性传染病,给全球养猪业造成了重大的经济损失。由于PEDV基因组的高易变性,开发有效的疫苗或药物来预防和控制PEDV仍然面临很大的困难。在本研究中,我们发现天然化合物姜黄素对VERO-E6和IPEC-J2细胞具有有效的抗病毒活性。通过转录组学方法筛选JAK-STAT信号通路作为IPEC-J2细胞抗PEDV感染的潜在先天免疫机制。对于PEDV这种高致病性病毒,细胞自身免疫反应不足以对抗其感染。结果表明,姜黄素可能通过增强IPEC-J2细胞中I型干扰素IFN-α和IFN-β介导的JAK-STAT级联反应而发挥抗病毒作用。体内实验进一步证实了姜黄素对pedv感染仔猪的保护作用及其对JAK-STAT信号通路的正向调节作用。在体内,姜黄素预防可显著增强IFN-α和IFN-β诱导的JAK-STAT信号和干扰素刺激基因(ISGs)的产生,增强先天免疫应答,从而有效发挥抗病毒作用。综上所述,我们的数据表明姜黄素能有效抵抗IPEC-J2细胞和仔猪PEDV感染,为抗PEDV药物的开发提供了新的参考,具有重要的应用前景。
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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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