Department of Biochemistry & Biotechnology, University of Barishal, Barishal, 8254, Bangladesh.
Department of Mathematics and Natural Sciences, BRAC University, Dhaka, Bangladesh.
Comput Biol Chem. 2021 Jun;92:107462. doi: 10.1016/j.compbiolchem.2021.107462. Epub 2021 Feb 19.
Chikungunya virus (CHIKV) that causes chikungunya fever, is an alphavirus that belongs to the Togaviridae family containing a single-stranded RNA genome. Mosquitoes of the Aedes species act as the vectors for this virus and can be found in the blood, which can be passed from an infected person to a mosquito through mosquito bites. CHIKV has drawn much attention recently because of its potential of causing an epidemic. As the detailed mechanism of its pathogenesis inside the host system is still lacking, in this in silico research we have hypothesized that CHIKV might create miRNAs, which would target the genes associated with host cellular regulatory pathways, thereby providing the virus with prolonged refuge. Using bioinformatics approaches we found several putative miRNAs produced by CHIKV. Then we predicted the genes of the host targeted by these miRNAs. Functional enrichment analysis of these targeted genes shows the involvement of several biological pathways regulating antiviral immune stimulation, cellular proliferation, and cell cycle, thereby provide themselves with prolonged refuge and facilitate their pathogenesis, which in turn may lead to disease conditions. Finally, we analyzed a publicly available microarray dataset (GSE49985) to determine the altered expression levels of the targeted genes and found genes associated with pathways such as cell differentiation, phagocytosis, T-cell activation, response to cytokine, autophagy, Toll-like receptor signaling, RIG-I like receptor signaling and apoptosis. Our finding presents novel miRNAs and their targeted genes, which upon experimental validation could facilitate in developing new therapeutics to combat CHIKV infection and minimize CHIKV mediated diseases.
基孔肯雅热病毒(CHIKV)是一种引起基孔肯雅热的阿尔法病毒,属于披膜病毒科,含有单链 RNA 基因组。埃及伊蚊等蚊子是该病毒的载体,可在血液中发现,通过蚊子叮咬可从感染者传播到蚊子。由于其潜在的流行潜力,CHIKV 最近引起了广泛关注。由于其在宿主系统内的发病机制的详细机制尚不清楚,在这项计算机研究中,我们假设 CHIKV 可能会产生 microRNA,这些 microRNA 将针对与宿主细胞调节途径相关的基因,从而为病毒提供长期避难所。我们使用生物信息学方法发现了几种由 CHIKV 产生的推定 microRNA。然后,我们预测了这些 microRNA 靶向的宿主基因。这些靶向基因的功能富集分析表明,参与了几个调节抗病毒免疫刺激、细胞增殖和细胞周期的生物途径,从而为自身提供了长期的避难所,并促进了它们的发病机制,进而可能导致疾病状态。最后,我们分析了一个公开的微阵列数据集(GSE49985),以确定靶向基因的改变表达水平,并发现与细胞分化、吞噬作用、T 细胞激活、细胞因子反应、自噬、Toll 样受体信号、RIG-I 样受体信号和凋亡等途径相关的基因。我们的发现提出了新的 microRNA 及其靶向基因,通过实验验证,这些基因可能有助于开发新的治疗方法来对抗 CHIKV 感染并最小化 CHIKV 介导的疾病。