Chen Zihan, Wang Jingyu, Lu Baochun, Meng Wenxin, Zhu Yufan, Jiang Qifeng, Gao Duo, Ma Zihang, Zeng Huijuan, Chen Jinping, Liu Shizhe, Wang Zhen, Jia Kun
College of Veterinary Medicine, South China Agricultural University, Guangdong, 510642, China.
College of Veterinary Medicine, Jilin University, Changchun, 130062, China.
Ir Vet J. 2025 Apr 2;78(1):10. doi: 10.1186/s13620-025-00286-3.
Bovine viral diarrhoea (BVD), a condition triggered by bovine viral diarrhoea virus (BVDV), is recognized globally as a prevalent pathogen among ruminants and markedly affects the economics of animal husbandry. MicroRNAs, a class of small noncoding RNAs, play pivotal roles in regulating a myriad of biological processes.The ATG7-LC3 pathway, a canonical autophagy mechanism, is integral in defending against pathogenic invasion and maintaining cellular homeostasis.
In this study, we observed significant downregulation of bta-miR-221 in cells infected with BVDV. We further established that overexpression of bta-miR-221 markedly attenuated BVDV replication in Madin‒Darby bovine kidney (MDBK) cells. Through bioinformatics prediction analysis, we identified ATG7, an autophagy-related gene, as a direct downstream target of bta-miR-221. However, the intricate relationships among bta-miR-221, the ATG7-LC3 pathway, and BVDV infection remained unclear. Our study revealed that ATG7 expression was significantly elevated in BVDV-infected cells, whereas bta-miR-221 mimics repressed both endogenous and exogenous ATG7 expression. Following BVDV infection, we noted a decrease in LC3I expression, its conversion to LC3II, a significant increase in ATG7 expression, and a notable decrease in SQSTM1/p62 expression. By employing laser confocal microscopy and immunoprecipitation assays, we elucidated the regulation of the ATG7-LC3 pathway by bta-miR-221 in MDBK cells. Our findings recealed that BVDV infection enhanced the ATG7-LC3 interaction, inducing autophagy through the suppression of bta-miR-221 in MDBK cells. Consequently, bta-miR-221 emerged as a potent inhibitor of BVDV, impacting its proliferation and replication within the host.
This research sheds light on novel aspects of virus-host interactions and lays a foundation for the development of antiviral therapeutics.
牛病毒性腹泻（BVD）是由牛病毒性腹泻病毒（BVDV）引发的一种疾病，在全球范围内被认为是反刍动物中普遍存在的病原体，对畜牧业经济有显著影响。微小RNA是一类小的非编码RNA，在调节众多生物过程中起关键作用。自噬相关基因7-微管相关蛋白轻链3（ATG7-LC3）途径是一种典型的自噬机制，在抵御病原体入侵和维持细胞稳态中不可或缺。
在本研究中，我们观察到感染BVDV的细胞中牛miR-221（bta-miR-221）显著下调。我们进一步证实，bta-miR-221的过表达显著减弱了Madin-Darby牛肾（MDBK）细胞中BVDV的复制。通过生物信息学预测分析，我们确定自噬相关基因ATG7是bta-miR-221的直接下游靶点。然而，bta-miR-221、ATG7-LC3途径和BVDV感染之间的复杂关系仍不清楚。我们的研究表明，BVDV感染细胞中ATG7表达显著升高，而bta-miR-221模拟物抑制内源性和外源性ATG7表达。BVDV感染后，我们注意到微管相关蛋白轻链3-I（LC3I）表达减少，其转化为微管相关蛋白轻链3-II（LC3II），ATG7表达显著增加，而 sequestosome 1/p62（SQSTM1/p62）表达显著减少。通过激光共聚焦显微镜和免疫沉淀试验，我们阐明了bta-miR-221在MDBK细胞中对ATG7-LC3途径的调控。我们的研究结果表明，BVDV感染增强了ATG7-LC3相互作用，通过抑制MDBK细胞中的bta-miR-221诱导自噬。因此，bta-miR-221成为BVDV的有效抑制剂，影响其在宿主体内的增殖和复制。
本研究揭示了病毒-宿主相互作用的新方面，为抗病毒治疗的发展奠定了基础。
