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gga-miR-200a-3p 通过靶向 GRB2 抑制禽呼肠孤病毒诱导的细胞凋亡和病毒复制。

Gga-miR-200a-3p suppresses avian reovirus-induced apoptosis and viral replication via targeting GRB2.

机构信息

National Key Laboratory of Veterinary Public Health Security, China; Animal Epidemiology of the Ministry of Agriculture, China; College of Veterinary Medicine, China Agricultural University, Beijing 100193, China.

National Key Laboratory of Veterinary Public Health Security, China; Animal Epidemiology of the Ministry of Agriculture, China; College of Veterinary Medicine, China Agricultural University, Beijing 100193, China.

出版信息

Vet Microbiol. 2024 Aug;295:110149. doi: 10.1016/j.vetmic.2024.110149. Epub 2024 Jun 12.

DOI:10.1016/j.vetmic.2024.110149
PMID:38909417
Abstract

Avian reovirus (ARV) is a significant pathogen that causes various clinical diseases in chickens, including viral arthritis, chronic respiratory diseases, retarded growth, and malabsorption syndrome. These conditions result in substantial economic losses for the global poultry industry. MicroRNAs (miRNAs), a type of small noncoding RNAs that regulate gene expression post transcriptionally by silencing or degrading their RNA targets, play crucial roles in response to pathogenic infections. In this study, transfection of DF-1 cells with gga-miR-200a-3p, an upregulated miRNA observed in ARV-infected cells, significantly suppressed ARV-induced apoptosis by directly targeting GRB2 and impeded ARV replication. Conversely, knockdown of endogenous gga-miR-200a-3p in DF-1 cells using a specific miRNA inhibitor enhanced ARV-induced apoptosis and promoted GRB2 expression, thereby facilitating viral growth within cells. Consistently, inhibition of GRB2 activity through siRNA-mediated knockdown reduced viral titers. Therefore, gga-miR-200a-3p plays a vital antiviral role in the host response to ARV infection by suppressing apoptosis via direct targeting of GRB2 protein. This information enhances our understanding of the mechanisms by which host cells combat against ARV infection through self-encoded small RNA molecules and expands our knowledge regarding the involvement of microRNAs in the host response to pathogenic infections.

摘要

禽呼肠孤病毒(ARV)是一种重要的病原体,可引起鸡的各种临床疾病,包括病毒性关节炎、慢性呼吸道疾病、生长迟缓以及吸收不良综合征。这些情况给全球家禽业造成了巨大的经济损失。microRNAs(miRNAs)是一类小的非编码 RNA,通过沉默或降解其 RNA 靶标来在后转录水平上调节基因表达,在应对致病感染中发挥着重要作用。在这项研究中,用在 ARV 感染细胞中上调的 miRNAgga-miR-200a-3p 转染 DF-1 细胞,通过直接靶向 GRB2 显著抑制了 ARV 诱导的细胞凋亡,并阻碍了 ARV 的复制。相反,用特异性 miRNA 抑制剂敲低 DF-1 细胞中的内源性 gga-miR-200a-3p,增强了 ARV 诱导的细胞凋亡并促进了 GRB2 的表达,从而促进了细胞内病毒的生长。同样,通过 siRNA 介导的敲低抑制 GRB2 活性降低了病毒滴度。因此,gga-miR-200a-3p 通过直接靶向 GRB2 蛋白抑制细胞凋亡,在宿主对 ARV 感染的反应中发挥着重要的抗病毒作用。这一信息增强了我们对宿主细胞通过自身编码的小 RNA 分子对抗 ARV 感染的机制的理解,并扩展了我们对 microRNAs 参与宿主对致病感染反应的认识。

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