Key Laboratory of Animal Epidemiology of the Ministry of Agriculture, China; College of Veterinary Medicine, China Agricultural University, Beijing, 100193, China.
College of Veterinary Medicine, China Agricultural University, Beijing, 100193, China.
Vet Microbiol. 2022 Jan;264:109294. doi: 10.1016/j.vetmic.2021.109294. Epub 2021 Nov 24.
Avian reovirus (ARV) is an important pathogen causing multiple types of clinical diseases in chickens, including viral arthritis, chronic respiratory diseases, retarded growth, and malabsorption syndrome, leading to considerable economic losses to the poultry industry across the globe. MicroRNAs (miRNAs) are small noncoding RNAs that regulate gene expression post transcriptionally by silencing or degrading their targets, thus playing important roles in the host response to pathogenic infection. However, the role of miRNAs in host response to ARV infection is still not clear. Here, we show that infection of DF-1 cells (a chicken fibroblast cell line) with ARV markedly altered the expressions of 583 chicken miRNAs(gga-miR), and that transfection of DF-1 cells with gga-miR-29a-3p, an upregulated miRNA in ARV-infected cells, significantly suppressed ARV-induced apoptosis via directly targeting Caspase-3, retarding ARV growth in cells. In contrast, knockdown of endogenous gga-miR-29a-3p in DF-1 cells by specific miRNA inhibitor enhanced ARV-induced apoptosis and increased the content and activity of caspase-3, facilitating viral growth in cells. Consistently, inhibition of Caspase-3 activity by inhibitors decreased viral titers in cell cultures. Thus, gga-miR-29a-3p plays an important antiviral role in host response to ARV infection by suppression of apoptosis via targeting Caspase-3. This information will further our understandings of how host cells combat against ARV infection by self-encoded small RNA and increase our knowledge of the role of microRNAs in host response to pathogenic infection.
禽呼肠孤病毒（ARV）是一种重要的病原体，可引起鸡的多种临床疾病，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，给全球家禽业造成了巨大的经济损失。微小 RNA（miRNA）是一类小的非编码 RNA，通过沉默或降解其靶标来进行转录后基因表达调控，因此在宿主对致病感染的反应中发挥着重要作用。然而，miRNA 在宿主对 ARV 感染的反应中的作用尚不清楚。在这里，我们表明 ARV 感染 DF-1 细胞（一种鸡成纤维细胞系）显著改变了 583 种鸡 miRNA（gga-miR）的表达，并且转染 DF-1 细胞gga-miR-29a-3p，一种在 ARV 感染细胞中上调的 miRNA，通过直接靶向 Caspase-3 显著抑制 ARV 诱导的细胞凋亡，从而延缓细胞中 ARV 的生长。相反，通过特异性 miRNA 抑制剂敲低 DF-1 细胞中的内源性 gga-miR-29a-3p 增强了 ARV 诱导的细胞凋亡，并增加了 Caspase-3 的含量和活性，促进了细胞中的病毒生长。一致地，抑制剂抑制 Caspase-3 活性降低了细胞培养物中的病毒滴度。因此，gga-miR-29a-3p 通过靶向 Caspase-3 抑制细胞凋亡在宿主对 ARV 感染的反应中发挥重要的抗病毒作用。这些信息将进一步加深我们对宿主细胞通过自身编码的小 RNA 对抗 ARV 感染的理解，并增加我们对 miRNA 在宿主对致病感染反应中的作用的认识。
