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计算机模拟中抗埃博拉微小RNA对埃博拉病毒的抑制作用

Inhibition of Ebola Virus by Anti-Ebola miRNAs in silico.

作者信息

Golkar Zhabiz, Battaria Roshan, Pace Donald G, Bagasra Omar

机构信息

School of Health and Natural Science, Voorhees College, Denmark, SC, United States.

出版信息

J Infect Dev Ctries. 2016 Jun 30;10(6):626-34. doi: 10.3855/jidc.7127.

Abstract

INTRODUCTION

MicroRNAs (miRNAs) are small, noncoding RNA molecules that regulate transcriptional and posttranscriptional gene regulation of the organisms. miRNA provides immune defense when the body is faced with challenges intracellular agents. miRNA molecules trigger gene silencing in eukaryotic cells. More than 3,000 different human miRNAs (hsa-miRs) have been identified thus far. During ontogenesis, viral or intracellular parasitic infections, miRNAs are differentially expressed to protect the host from intracellular invaders. In a viral infection context, miRNAs have been connected with the interplay between host and pathogen, and occupy a major role in pathogenesis.

METHODOLOGY

An in silico approach was used to analyze the four major Ebola Virus genome sequences including the recently characterized Ebola virus responsible for West African epidemic that has killed over 10,000 people. All totaled, 2,543 mature human miRNA sequences were retrieved through an miR-database, and the identification of mature miRNAs were aligned with full length sequences of the four major Ebola viruses via computational tools.

RESULTS

We identified 32 miRNAs that exhibited significant inhibitory capacity to block more than one EBV strains. miR-607 showed capacity to quell all four major EBVs. Ten putative miRNAs were found to have near perfect identity at seed sequences with numerous targets of Ebola virus that may completely degrade the viral transcripts.

CONCLUSION

We hypothesize that a miRNA-based vaccine can quell Ebola virus infection. Future approaches will focus on validation of these miRNAs in quelling the Ebola virus to further elucidate their biological functions in primate and other animal models.

摘要

引言

微小RNA(miRNA)是小型非编码RNA分子,可调节生物体的转录和转录后基因调控。当身体面临细胞内病原体挑战时,miRNA提供免疫防御。miRNA分子在真核细胞中引发基因沉默。迄今为止,已鉴定出3000多种不同的人类miRNA(hsa-miR)。在个体发育、病毒或细胞内寄生虫感染期间,miRNA差异表达以保护宿主免受细胞内入侵者侵害。在病毒感染背景下,miRNA与宿主和病原体之间的相互作用有关,并在发病机制中起主要作用。

方法

采用计算机分析方法,分析包括最近导致西非疫情(已造成1万多人死亡)的埃博拉病毒在内的四种主要埃博拉病毒基因组序列。通过miR数据库总共检索到2543条成熟人类miRNA序列,并使用计算工具将成熟miRNA的鉴定结果与四种主要埃博拉病毒的全长序列进行比对。

结果

我们鉴定出32种对不止一种埃博拉病毒株具有显著抑制能力的miRNA。miR-607显示出抑制所有四种主要埃博拉病毒的能力。发现10种假定的miRNA在种子序列上与埃博拉病毒的众多靶标具有近乎完美的一致性,这可能会完全降解病毒转录本。

结论

我们推测基于miRNA的疫苗可以抑制埃博拉病毒感染。未来的研究将集中在验证这些miRNA在抑制埃博拉病毒方面的作用,以进一步阐明它们在灵长类动物和其他动物模型中的生物学功能。

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