Chrysin通过ROS/JNK/p53轴拮抗凋亡抑制PEDV复制。

IF 3.5 3区 医学 Q3 IMMUNOLOGY
Microbial pathogenesis Pub Date : 2025-11-01 Epub Date: 2025-08-06 DOI:10.1016/j.micpath.2025.107957
Yupeng Zhi, Yupeng Ren, Xuemei Xia, Qiao Tian, Yingshi Meng, Siyu Tao
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引用次数: 0

摘要

猪流行性腹泻病毒(PEDV)仍然是全球养猪业的重大威胁,其免疫策略受到病毒基因组变异和缺乏有效治疗药物的限制。黄酮类化合物菊花素显示出潜在的抗pedv活性,但其具体的抗病毒机制尚不清楚。本研究通过IFA和qPCR验证了菊花素对PEDV的抑制作用。此外,对pedv感染的Vero细胞进行转录组测序,以揭示其抗病毒机制。结果显示,在12 hpi和24 hpi位点分别有5813和3374个deg,富集于转录、翻译、代谢、先天免疫和凋亡相关通路。值得注意的是,KEGG分析表明,Chrysin通过调节TNF、MAPK和p53信号通路来调节PEDV诱导的细胞凋亡,这可能拮抗PEDV感染。随后的研究结果证实,菊花素可以显著下调PEDV感染诱导的活性氧水平和细胞凋亡率(P
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Chrysin inhibits PEDV replication by antagonizing apoptosis via the ROS/JNK/p53 axis.

Porcine epidemic diarrhea virus (PEDV) remains a significant threat to global swine industry, with immunization strategies limited by viral genome variation and a lack of effective therapeutic drugs. The flavonoid compound chrysin has shown potential anti-PEDV activity, but its specific antiviral mechanisms remain unclear. This study validated the inhibitory effect of chrysin on PEDV using IFA and qPCR. Additionally, Transcriptome sequencing was conducted on PEDV-infected Vero cells with and without chrysin treatment to reveal its antiviral mechanism. The results showed that 5813 DEGs at 12 hpi and 3374 DEGs at 24 hpi, with enrichment in pathways related to transcription, translation, metabolism, innate immunity, and apoptosis. Notably, KEGG analysis indicated that Chrysin regulate PEDV-induced apoptosis by modulating the TNF, MAPK, and p53 signaling pathways, which might antagonize PEDV infection. Subsequent results confirmed that chrysin can significantly downregulate the reactive ROS levels and cell apoptosis rate induced by PEDV infection (P<0.05), and inhibit the activation of the JNK and p53 pathways, including the phosphorylation of ASK1, JNK, and p53. Chrysin also significantly reduced cleaved caspase 3/8/9 levels and Bax/Bcl-2 ratios, thereby affecting PEDV N protein expression (P < 0.05). Moreover, similar inhibitory effects on PEDV can also be achieved through the JNK inhibitor SP600125 and the p53 inhibitor PFT-α. These findings revealed that chrysin can antagonize PEDV-induced apoptosis through the ROS/JNK/p53 signaling axis, thereby inhibiting viral replication. This study provides a scientific basis for developing chrysin as a novel anti-PEDV drug and offers insights into the screening and research of antiviral drug targets.

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来源期刊
Microbial pathogenesis
Microbial pathogenesis 医学-免疫学
CiteScore
7.40
自引率
2.60%
发文量
472
审稿时长
56 days
期刊介绍: Microbial Pathogenesis publishes original contributions and reviews about the molecular and cellular mechanisms of infectious diseases. It covers microbiology, host-pathogen interaction and immunology related to infectious agents, including bacteria, fungi, viruses and protozoa. It also accepts papers in the field of clinical microbiology, with the exception of case reports. Research Areas Include: -Pathogenesis -Virulence factors -Host susceptibility or resistance -Immune mechanisms -Identification, cloning and sequencing of relevant genes -Genetic studies -Viruses, prokaryotic organisms and protozoa -Microbiota -Systems biology related to infectious diseases -Targets for vaccine design (pre-clinical studies)
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