Computational analysis to predict role of human microRNAs in Ebola virusgenome

The Ebola virus (EBOV)is already listed as a top categories pathogen by several organizations including WHO, CDC and NIH because fatality rate is up to ninety percent [4,7]. It is a member of Filoviridae family that causes fatal hemorrhagic fever including both human and non-human primates [1-3]. Several reports suggested that susceptible hosts can be died by most virulent species within ten days after the appearance of symptoms [4-5]. The first case of Ebola virus was reported in 1976 on the Africa region [6]. Five (5) different species of Ebola viruses have been reported so far. Among these except Reston, REBOV, all 4 are being capable of causing diseases in human [8-9]. As Ebola virus is enveloped, non-segmented, negative-strand RNA viruses and genome size approximately 19 kb in length, it has high fatality rate and easily transmissible [10-11]. The viral genome encodes seven structural proteins and one non-structural protein while viral proteins perform different functions including viral replication [11].

The miRNAs are small non-coding RNA molecule, genomically encoded, usually around twenty-two base pair in length and regulate genes expression at the post-transcriptional level either mRNA degradation or repress translation [12-14]. It is well documented that miRNAs operate their different biological or physiological functions including apoptosis, development, tumorigenesis, stress response, proliferation and fat metabolism [15-16]. Although, current monoclonal antibody (mAb) based therapies are thought to the most efficient against lethal Ebola virus infection in non-human primates. In this research study, we have proposed miRNA-based gene silencing activity as a suitable alternative, in addition to current vaccine mediate treatment.

Viral miRNAs are unique because it regulates both their own gene expression and host gene expression [18]. MiRNA genes are firstly transcribed into primary miRNA. Then they are cleaved by enzymatic activity of the RNase III ribonuclease Drosha into 60-90 base pair long hairpin intermediate known as pre-miRNA [18-20]. By the action of enzyme exportin-5 and ran pre-miRNAs are exported from nucleus to cytoplasm [19]. The pre-miRNAs are further cleaved by Drosha (another RNase III ribonuclease) in the cytoplasm and are formed into a double stranded RNA known as duplex mature RNA [19].RNA-induced silencing complex (RISC) that is one strand (guided strand) of duplex RNA, targets messenger RNA to degrade or repress translational activity [18].