Comprehensive computational analysis reveals human respiratory syncytial virus encoded microRNA and host specific target genes associated with antiviral immune responses and protein binding

Abstract

Objective: About half-century ago, human respiratory syncytial virus (hRSV) was observed in infants and children under age of five years. As the mechanism of its pathogenesis inside the host is still lacking, in this in-silico study we hypothesized that RSV might create miRNAs, which could target the genes associated with host cellular regulatory pathways, thus provide persistent refuge to virus. Methodology: Pre-miRNAs in RSV genome (accession no. NC_001803.1) were extracted through VMir software, and the identification of putative pre-miRNAs and mature miRNAs was accessed using iMiRNA-SSF and FOMmiR tool, respectively. Later, prediction of host specific target gene was accompanied by RNAhybrid tool. Moreover, bioinformatics analysis was done for the validation of target genes using microarray dataset (GSE80179). Lastly, Drug-gene interaction database was used to explore the small drug like candidate against RSV infection. Results: Searching RSV genome for their pre-miRNAs yielded 15 pre-miRNAs like sequence with length vary for each pre-miRNA sequences. FOMmiR tool revealed a total of 7 mature miRNAs from 6 real pre-miRNA hairpins. Functional enrichment analysis of targeted genes, revealed their involvement in many biological pathways which facilitate their pathogenesis in host. The microarray dataset (GSE80179) was analyzed to validate altered expression level of target genes and found genes linked with pathways such as T-cell activation, apoptosis, NF-kappa B signaling, cell differentiation and autophagy. CYCS, CTLA4, and BTK were chosen as possible targets of 21 drugs. A total of 21 drugs were explored using DGIdb that might have potential to treat RSV patient. Conclusion: This study updates the information and yield a new perspective in context of understanding the pathogenesis of RSV. Our study presents novel miRNAs and their targeted hub genes, which upon experimental validation could facilitate in developing new therapeutics against RSV infection. In vivo and in vitro investigation of miRNAs and pathway interaction is essential to delineate the specific roles of the novel miRNAs, which may help to reveal the mechanisms behind the pathogenesis. Based on the hub genes and miRNAs, experimental models may be designed in terms of the detection of pathogenesis, evaluation of risk, and determining the targeted therapies of RSV infections.

Keywords

• In silico analysis
• Respiratory syncytial virus
• miRNA
• Hub genes
• Pathway analysis
• Gene expression profiling