Najib Abdellaoui, Kim Min Sun, Kim Ki Hong
Department of Aquatic Life Medicine, Pukyong National University, Busan 48513, Republic of Korea.
Graduate School of Integrated Bioindustry, Sejong University, Seoul 05006, Republic of Korea.
Fish Shellfish Immunol. 2017 Feb;61:93-99. doi: 10.1016/j.fsi.2016.12.022. Epub 2016 Dec 20.
MicroRNAs are small non-coding RNAs and are involved in the regulation of wide biological processes. Viral hemorrhagic septicemia virus (VHSV) is the causative agent of viral hemorrhagic septicemia (VHS) disease causing a heavy loss in aquaculture farms. In this study, we tried to explore the effect of VHSV infection on microRNAs profile of Epithelioma papulosum cyprini (EPC) cells at different points of time (0, 3, 12, 24, and 48 h post infection). A total of 355 conserved microRNAs and 3 novel microRNAs were identified, and among them, 103 microRNAs were differentially expressed. The number of differentially expressed microRNAs was highly increased at 24 h.p.i compared to 3 h.p.i and 12 h.p.i., suggesting that EPC cells might not actively respond to VHSV infection at an early infection period, which can allow viruses to transcript and translate their genes enough to produce viral particles that can infect to another cells. Among the differentially expressed microRNAs, 2 miRNAs (miR-735 and miR-738) that were reported only in fish species were highly upregulated, and based on the target prediction, they could regulate several immune pathways. Furthermore, the present results showed the upregulation of representative immune regulating microRNAs such as miR-146a, miR-155, and miR-99. The target prediction of differentially expressed miRNAs, GO, and KEGG pathways analysis revealed that several biological processes and different pathways were affected by the viral infection. The present dynamical changing patterns of differentially expressed microRNAs in response to the progression of VHSV infection suggest that microRNA profile that was analyzed at one time point cannot provide enough information for the interpretation of the disease mechanism. Considering the wide and complex interactions between microRNAs and genes expression, the present results provide the basis for the understanding of VHSV infection-mediated cellular responses and for future investigations on the development of possible control measures.
微小RNA是一类小的非编码RNA，参与广泛的生物学过程调控。病毒性出血性败血症病毒（VHSV）是病毒性出血性败血症（VHS）疾病的病原体，给水产养殖场造成了巨大损失。在本研究中，我们试图探究VHSV感染在不同时间点（感染后0、3、12、24和48小时）对鲤上皮瘤（EPC）细胞微小RNA谱的影响。共鉴定出355个保守微小RNA和3个新的微小RNA，其中103个微小RNA差异表达。与感染后3小时和12小时相比，感染后24小时差异表达的微小RNA数量大幅增加，这表明EPC细胞在感染早期可能不会对VHSV感染产生积极反应，这使得病毒能够充分转录和翻译其基因以产生可感染其他细胞的病毒颗粒。在差异表达的微小RNA中，仅在鱼类中报道的2个微小RNA（miR - 735和miR - 738）高度上调，基于靶标预测，它们可调控多种免疫途径。此外，本研究结果还显示了代表性免疫调节微小RNA如miR - 146a、miR - 155和miR - 99的上调。差异表达微小RNA的靶标预测、基因本体（GO）和京都基因与基因组百科全书（KEGG）通路分析表明，病毒感染影响了多个生物学过程和不同通路。VHSV感染过程中差异表达微小RNA的这种动态变化模式表明，在一个时间点分析的微小RNA谱不足以解释疾病机制。考虑到微小RNA与基因表达之间广泛而复杂的相互作用，本研究结果为理解VHSV感染介导的细胞反应以及未来开发可能的控制措施的研究提供了基础。
