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细胞 microRNA,miR-1343-5p,通过直接靶向 IRAK1 基因调节 IFN-I 反应,促进猫泛白细胞减少症病毒复制。

Cellular microRNA, miR-1343-5p, modulates IFN-I responses to facilitate feline panleukopenia virus replication by directly targeting IRAK1 gene.

机构信息

Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing, 100193, China; Scientific Observation and Experiment Station of Veterinary Drugs and Diagnostic Technology of Beijing, Ministry of Agriculture, Beijing, 100193, China.

Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing, 100193, China; Scientific Observation and Experiment Station of Veterinary Drugs and Diagnostic Technology of Beijing, Ministry of Agriculture, Beijing, 100193, China.

出版信息

Vet Microbiol. 2020 Jun;245:108691. doi: 10.1016/j.vetmic.2020.108691. Epub 2020 Apr 19.

Abstract

Feline panleukopenia is an acute, highly contagious, and fatal infectious disease caused by feline panleukopenia virus (FPV) and has led to severe consequences on pets, economically important animals, and the wildlife industry. MicroRNAs (miRNAs) play significant roles in the host-pathogen interaction by modulating cellular factors expression which are essential for viral replication or host innate immune response to infection. However, the role of host miRNA response in FPV infection remains to be discovered. In this study, we screened nine host miRNAs associated with FPV infection that were previously implicated in innate immunity or antiviral functions. We found that miR-1343-5p overexpression strongly promoted FPV-BJ04 genomic DNA. Subsequently, the expression of host miR-1343-5p was upregulated by FPV-BJ04 infection in vitro and in vivo. In addition, we demonstrated that miR-1343-5p was a negative regulator of the IFN-I signaling pathway, thereby promoting FPV infection. Bioinformatic analysis combined with molecular biological assay indicated that interleukin-1 receptor-associated kinase 1 (IRAK1) is a putative target of miR-1343-5p. Collectively, our findings emphasize the importance of miR-1343-5p in host defense against FPV, thus, enhancing our understanding of its pathogenic mechanism.

摘要

猫泛白细胞减少症是一种由猫泛白细胞减少症病毒(FPV)引起的急性、高度传染性和致命性传染病,对宠物、经济重要动物和野生动物产业造成了严重后果。MicroRNAs(miRNAs)通过调节对病毒复制或宿主固有免疫反应至关重要的细胞因子表达,在宿主-病原体相互作用中发挥重要作用。然而,宿主 miRNA 反应在 FPV 感染中的作用仍有待发现。在这项研究中,我们筛选了与先前涉及先天免疫或抗病毒功能相关的 9 种与 FPV 感染相关的宿主 miRNAs。我们发现 miR-1343-5p 的过表达强烈促进了 FPV-BJ04 基因组 DNA 的复制。随后,我们在体外和体内证实了 FPV-BJ04 感染后宿主 miR-1343-5p 的表达上调。此外,我们证明了 miR-1343-5p 是 IFN-I 信号通路的负调节剂,从而促进了 FPV 的感染。生物信息学分析结合分子生物学检测表明,白细胞介素 1 受体相关激酶 1(IRAK1)是 miR-1343-5p 的一个假定靶点。总之,我们的研究结果强调了 miR-1343-5p 在宿主抵抗 FPV 中的重要性,从而加深了我们对其致病机制的理解。

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