Abstract

Recently, several thousand people have been killed by the Ebolavirus disease (EVD) in West Africa, yet no current antiviral medications and treatments are available. Systematic investigation of ebolavirus whole genomes during the 2014 outbreak may shed light on the underlying mechanisms of EVD development. Here, using the genome-wide screening in ebolavirus genome sequences, we predicted four putative viral microRNA precursors (pre-miRNAs) and seven putative mature microRNAs (miRNAs). Combing bioinformatics analysis and prediction of the potential ebolavirus miRNA target genes, we suggest that two ebolavirus coding possible miRNAs may be silence and down-regulate the target genes NFKBIE and RIPK1, which are the central mediator of the pathways related with host cell defense mechanism. Additionally, the ebolavirus exploits the miRNAs to inhibit the NF-kB and TNF factors to evade the host defense mechanisms that limit replication by killing infected cells, or to conversely trigger apoptosis as a mechanism to increase virus spreading. This is the first study to use the genome-wide scanning to predict microRNAs in the 2014 outbreak EVD and then to apply systematic bioinformatics to analyze their target genes. We revealed a potential mechanism of miRNAs in ebolavirus infection and possible therapeutic targets for Ebola viral infection treatment.

Highlights

  • The genus Ebolavirus belongs to the family Filoviridae and order Mononegavirales, where the members of this genus are called ebolaviruses[1]

  • The sequences of the eight mature EBOV miRNAs are listed in Table 2, where EBV-miR-T3-5p has the same sequence with EBV-miR-T4-5p

  • From March 2014 to October 2014, the largest EBOV outbreak in the history has killed several thousand people in West Africa, yet no current specific treatment is validated for EBOV. miRNAs has been demonstrated to circulate in a highly stable, cell-free form in body fluids circulating miRNAs can be used as non-invasive biomarkers for molecular diagnostics and prognostics[24]

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Summary

Introduction

The genus Ebolavirus belongs to the family Filoviridae and order Mononegavirales, where the members of this genus are called ebolaviruses[1]. From March 2014 to October 2014, the Ebola outbreak in West Africa has sickened 8,399 people, killing 4,033 of them[3] This is the largest EBOV outbreak in the history[4]. Several thousand people from affected areas travel to the North America, and even more travellers enter and leave Europe, other parts of Africa, and Asia[5] Such air travel situations increase the possibility of EVD transmission. To the best of our knowledge, this is the first paper to systemic genome-wide analyze and predict the potential non-coding RNAs in the 2014 outbreak EBOVs along with their target genes. Our research helps to further assess the roles of the 2014 outbreak EBOV miRNAs and their potential targets during viral infection and virus-host interactions, and to speed up the process of effective EVD treatment development

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