Decoding miRNA-Mediated Immunoregulation in SARS-CoV-2, HBV, HIV, and HSV Infections

Abstract Eukaryotic cells regulate gene expression through multiple checkpoints, including post-transcriptional mechanisms mediated by microRNAs (miRNAs). These small non-coding RNAs inhibit translation by binding to target mRNAs, often within a complex regulatory network involving other RNA species such as circular RNAs and long non-coding RNAs. miRNAs are now recognised as central players in the pathogenesis, immune modulation, and progression of infectious diseases. In this review, we thoroughly examine studies published over the past five years, focusing on miRNAs involved in immune regulation during four major viral infections: severe acute respiratory syndrome coronavirus 2, hepatitis B virus, human immunodeficiency virus, and herpes simplex virus. Our analysis centres on the core signalling pathways most frequently targeted by miRNAs: NF-κB, MAPK, JAK-STAT, TGF-β/Smad, and pattern-recognition receptor-associated cascades. Among the miRNAs most prominently implicated are miR-21, miR-146a, miR-150, and miR-155. These miRNAs modulate key signalling pathways, thereby influencing macrophage polarisation, T- and natural killer cell activity, antigen presentation, and inflammatory cytokine production. In addition, virus-encoded miRNAs and ceRNA or extracellular vesicle-mediated interactions are discussed where mechanistically validated, illustrating virus-specific regulatory layers. Collectively, this integrative synthesis underscores the pivotal roles of miRNAs in orchestrating antiviral immunity and highlights their potential as biomarkers and therapeutic targets in viral infections. A better understanding of miRNA-mediated immunoregulation may pave the way for precision interventions aimed at improving immune control and patient outcomes.