Role of miRNAs in Dengue Immunopathogenesis

Dengue is the most prevalent mosquito-borne viral disease in humans, with more than 50 million cases of dengue virus (DENV) infection each year. Dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS) are characterized by increased vascular permeability and plasma leakage. Recently, microRNAs (miRNAs) have been shown to modulate the innate and adaptive immune responses. Mounting evidence also supports the involvement of miRNAs in endothelial cell function.

Central hypothesis

miRNAs modulate the activation of monocytes/macrophages and vascular endothelial cells during DENV infection, and differential miRNA expression induced by DENV is associated with specific immunopathogenetic processes in DHF/DSS.

Objective

To characterize DENV-host interactions at the molecular level by performing functional analysis of miRNAs in DENV-infected cells.

Specific Aim 1

Functional analysis of miRNAs in DENV-infected human monocytes/macrophages.

Specific Aim 2

Functional analysis of miRNAs in DENV-infected human vascular endothelial cells.