The Role of MicroRNA Profiles in Antibody-Dependent Enhancement during Dengue Infection: Impact on Disease Severity and Therapeutic Approaches

Dengue virus is a major mosquito-borne pathogen that causes clinical manifestations ranging from asymptomatic infection to severe dengue, including dengue hemorrhagic fever and dengue shock syndrome. Disease severity is strongly associated with antibody-dependent enhancement (ADE), in which pre-existing non-neutralizing antibodies promote Fcγ receptor-mediated viral entry into immune cells, resulting in enhanced viral replication, immune dysregulation, endothelial dysfunction, and vascular leakage. Emerging evidence indicates that microRNAs (miRNAs) are key post-transcriptional regulators of host immune responses, inflammatory signaling, and vascular integrity during dengue virus infection. This review summarizes current evidence on the interplay between ADE and miRNA-mediated regulation of dengue pathogenesis, with emphasis on innate and adaptive immunity, Fcγ receptor signaling, cytokine responses, and endothelial barrier dysfunction. We also highlight circulating and tissue-specific miRNAs with potential value as biomarkers for disease severity and prognosis, and discuss emerging miRNA-based therapeutic strategies, including miRNA mimics and inhibitors, as host-directed approaches to modulate ADE-associated pathways. Improved understanding of miRNA regulatory networks may facilitate the development of novel biomarkers and targeted therapeutic strategies for severe dengue.