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外泌体 miRNA-328-3p 靶向 ZO-3 并抑制猪流行性腹泻病毒增殖。

Exosomal miRNA-328-3p targets ZO-3 and inhibits porcine epidemic diarrhea virus proliferation.

机构信息

College of Veterinary Medicine, Jilin Agricultural University, Changchun, 130118, China.

Jilin Provincal Center for Animal Disease Control and Prevention, Changchun, 130117, Jilin, China.

出版信息

Arch Virol. 2022 Mar;167(3):901-910. doi: 10.1007/s00705-022-05364-3. Epub 2022 Feb 11.

Abstract

As essential transfer carriers for cell-to-cell communication and genetic material, exosomes carry microRNAs that participate in the regulation of various biological processes. MicroRNAs are a type of single-stranded noncoding RNA that bind to specific target gene mRNAs to degrade or inhibit their translation, thereby regulating target gene expression. Although it is known that a variety of microRNAs are involved in the viral infection process, there are few reports on specific microRNAs involved in porcine epidemic diarrhea virus (PEDV) infection. In this study, we isolated and identified exosomes in PEDV-infected Vero E6 cells. Using transcriptomics technology, we found that miRNA-328-3p was significantly downregulated in exosomes following PEDV infection. Moreover, exosomal miRNA-328-3p inhibited infection by PEDV by targeting and inhibiting tight junction protein 3 (TJP-3/ZO-3) in recipient cells. Our findings provide evidence that, after infecting cells, PEDV downregulates expression of miRNA-328-3p, and the resulting reduced inhibition of the target protein ZO-3 helps to enhance PEDV infection. These results provide new insight for understanding the regulatory mechanism of PEDV infection.

摘要

作为细胞间通讯和遗传物质的重要载体,外泌体携带参与调节各种生物过程的 microRNAs。MicroRNAs 是一种单链非编码 RNA,可与特定靶基因 mRNAs 结合,降解或抑制其翻译,从而调节靶基因表达。尽管已知多种 microRNAs 参与病毒感染过程,但关于特定 microRNAs 参与猪流行性腹泻病毒(PEDV)感染的报道较少。在本研究中,我们从 PEDV 感染的 Vero E6 细胞中分离和鉴定了外泌体。使用转录组学技术,我们发现 PEDV 感染后外泌体中的 miRNA-328-3p 显著下调。此外,外泌体 miRNA-328-3p 通过靶向和抑制受体细胞中的紧密连接蛋白 3(TJP-3/ZO-3)来抑制 PEDV 感染。我们的研究结果表明,PEDV 感染细胞后会下调 miRNA-328-3p 的表达,而靶蛋白 ZO-3 的抑制减少有助于增强 PEDV 感染。这些结果为理解 PEDV 感染的调控机制提供了新的见解。

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