Li Pin-Hong, Wang Li-Qun, He Jia-Yang, Zhu Xiang-Long, Huang Wei, Wang Shao-Wen, Qin Qi-Wei, Sun Hong-Yan
University Joint Laboratory of Guangdong Province, Hong Kong and Macao Region on Marine Bioresource Conservation and Exploitation, College of Marine Sciences, South China Agricultural University, Guangzhou, China.
Southern Marine Science and Engineering Guangdong Laboratory, Zhuhai, China.
Front Immunol. 2021 Nov 10;12:767813. doi: 10.3389/fimmu.2021.767813. eCollection 2021.
Viral infections seriously affect the health of organisms including humans. Now, more and more researchers believe that microRNAs (miRNAs), one of the members of the non-coding RNA family, play significant roles in cell biological function, disease occurrence, and immunotherapy. However, the roles of miRNAs in virus infection (entry and replication) and cellular immune response remain poorly understood, especially in low vertebrate fish. In this study, based on the established virus-cell infection model, Singapore grouper iridovirus (SGIV)-infected cells were used to explore the roles of miR-124 of , an economically mariculture fish in southern China and Southeast Asia, in viral infection and host immune responses. The expression level of miR-124 was significantly upregulated after SGIV infection; miR-124 cannot significantly affect the entry of SGIV, but the upregulated miR-124 could significantly promote the SGIV-induced cytopathic effects (CPEs), the viral titer, and the expressions of viral genes. The target genes of miR-124 were JNK3/p38α mitogen-activated protein kinase (MAPK). Overexpression of miR-124 could dramatically inhibit the activation of NF-κB/activating protein-1 (AP-1), the transcription of proinflammatory factors, caspase-9/3, and the cell apoptosis. And opposite results happen when the expression of miR-124 was inhibited. The results suggest that miR-124 could promote viral replication and negatively regulate host immune response by targeting JNK3/p38α MAPK, which furthers our understanding of virus and host immune interactions.
病毒感染严重影响包括人类在内的生物体健康。如今,越来越多的研究人员认为,非编码RNA家族成员之一的微小RNA(miRNA)在细胞生物学功能、疾病发生和免疫治疗中发挥着重要作用。然而,miRNA在病毒感染(进入和复制)及细胞免疫反应中的作用仍知之甚少,尤其是在低等脊椎动物鱼类中。在本研究中,基于已建立的病毒-细胞感染模型,利用感染新加坡石斑鱼虹彩病毒(SGIV)的细胞,来探究中国南方和东南亚经济养殖鱼类石斑鱼的miR-124在病毒感染和宿主免疫反应中的作用。SGIV感染后,miR-124的表达水平显著上调;miR-124不能显著影响SGIV的进入,但上调的miR-124可显著促进SGIV诱导的细胞病变效应(CPE)、病毒滴度及病毒基因的表达。miR-124的靶基因是JNK3/p38α丝裂原活化蛋白激酶(MAPK)。miR-124的过表达可显著抑制NF-κB/活化蛋白-1(AP-1)的激活、促炎因子的转录、半胱天冬酶-9/3及细胞凋亡。而抑制miR-124的表达则会产生相反的结果。结果表明,miR-124可通过靶向JNK3/p38α MAPK促进病毒复制并负向调节宿主免疫反应,这进一步加深了我们对病毒与宿主免疫相互作用的理解。