Porcine circovirus type 2 ORF5 induces an inflammatory response by up-regulating miR-21 levels through targeting nuclear ssc-miR-30d

文献类型: 外文期刊

第一作者: Li, Chang

作者: Li, Chang;Yang, Keli;Song, Haofei;Xia, Chuqiao;Wu, Qiong;Zhu, Jiajia;Liu, Wei;Gao, Ting;Guo, Rui;Liu, Zewen;Yuan, Fangyan;Tian, Yongxiang;Zhou, Danna

作者机构:

关键词: Porcine circovirus type 2; ORF5; Nuclear ssc-miR-30d; Ssc-miR-21; Inflammatory response

期刊名称:VIRUS RESEARCH ( 影响因子:2.5; 五年影响因子:3.2 )

ISSN: 0168-1702

年卷期: 2024 年 346 卷

页码:

收录情况: SCI

摘要: Porcine circovirus type 2 (PCV2) infection leads to multi -system inflammation in pigs, and this effect can be achieved by upregulating host miR-21. The underlying mechanism of miR-21 regulates PCV2-induced inflammation is already known, however, how PCV2 regulates miR-21 levels and function using both autonomic and host factors remains to be further revealed. Here we present the first evidence that PCV2 ORF5 induces an inflammatory response by up-regulating miR-21 level through targeting nuclear miR-30d. In this study, we found that overexpression of ORF5 significantly increased miR-21 level and promoted the expression of inflammatory cytokines and activation of the NF- kappa B pathway, while ORF5 mutation had the opposite effect. Moreover, the differential expression of miR-21 could significantly change the pro-inflammatory effect of ORF5, indicating that ORF5 promotes inflammatory response by up-regulating miR-21. Bioinformatics analysis and clinical detection found that nuclear miR-30d was significantly down-regulated after ORF5 overexpression and PCV2 infection, and targeted pri-miR-21 and PCV2 ORF5. Functionally, we found that miR-30d inhibited the levels of miR-21 and inflammatory cytokines in cells. Mechanistically, we demonstrated that ORF5 inhibits miR-30d expression levels through direct binding but not via the circRNA pathway, and miR-30d inhibits miR-21 levels by targeting primiR-21. In summary, the present study revealed the molecular mechanism of ORF5 upregulation of miR-21, further refined the molecular chain of PCV2-induced inflammatory response and elucidated the role of miRNAs in it.

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