Unraveling the Dynamics of Dengue Infection: Analysis from Microarray, Highthroughput sequencing and Systems Biology

Abstract

Dengue, a mosquito-borne viral infection, poses a significant global health threat with no specific antiviral treatments available. Despite its widespread prevalence, the precise mechanisms underlying disease pathogenesis remain elusive, hindering the development of effective interventions. This research seeks to shed light on these mysteries by harnessing the power of advanced bioinformatics tools like microarray analysis, RNA sequencing, and single-cell technologies. Our primary objective is to identify differentially expressed genes (DEGs) and transcripts within the mRNA repertoire associated with dengue infection. This comprehensive analysis revealed key pathways significantly impacted by these DEGs, shedding light on the underlying mechanisms of the disease. Notably, genes like ITGb2, RBM39, and HSPA5 emerged as key players in differentiating the host immune response during dengue. To further explore the dynamic behavior of these genes, a mathematical model of the host immune signaling pathway was constructed and simulated. This enabled a closer examination of the ISRE element’s response, crucial for antiviral defense. Interestingly, HSPA5 exhibited a "dual role," both inhibiting and promoting viral replication, highlighting its complex regulatory function. These findings provide valuable insights into the intricate interplay between gene expression and the immune response in dengue. The identification of key genes and pathways, along with the exploration of HSPA5’s dual role, paves the way for the development of novel therapeutic strategies and preventative measures. Specifically, targeting HSPA5 as a regulator of INFalpha-beta holds promise for enhancing the immune response and effectively combating dengue infection. Additionally, exploring the role of other significant genes and their interactions with the immune signaling could lead to even more promising therapeutic avenues. This research contributes to the ongoing battle against dengue fever, offering hope for enhanced patient outcomes and improved global health