Comprehensive computational analysis reveals H5N1 influenza virus-encoded miRNAs and host-specific targets associated with antiviral immune responses and protein binding

Abstract

H5N1 virus (H5N1V) is highly contagious among birds and it was first detected in humans in 1997 during a poultry outbreak in Hong Kong. As the mechanism of its pathogenesis inside the host is still lacking, in this in-silico study we hypothesized that H5N1V might create miRNAs, which could target the genes associated with host cellular regulatory pathways, thus provide persistent refuge to the virus. Using bioinformatics approaches, several H5N1V produced putative miRNAs as well as the host genes targeted by these miRNAs were found. Functional enrichment analysis of targeted genes revealed their involvement in many biological pathways that facilitate their host pathogenesis. Eventually, the microarray dataset (GSE28166) was analyzed to validate the altered expression level of target genes and found the genes involved in protein binding and adaptive immune responses. This study presents novel miRNAs and their targeted genes, which upon experimental validation could facilitate in developing new therapeutics against H5N1V infection.

Fig 1. Graphical synopsis of representing the overall strategy used in the prediction of miRNA and their cellular targets.

Fig 2. Minimum free‐energy (MFE) value in RNAstructure webserver and the MFE secondary structure and positional entropy of 9 real pre-miRNAs were created.

(A) MD96; (B) MR124; (C) MR46; (D) MD105; (E) MD76 (F)MR90 (G) MD94 (H) MR64 (I) MD101.

Fig 3. The PPI network of the eight genes, and their related genes, created by the FunRich software.

Red nodes represents eight significant genes filtered through gene expression analysis, while green nodes represents neighboring genes of the eight genes.