Abstract
Dengue virus (DENV) is a major global health concern, with pathogenesis driven by complex interactions between the virus, host genetics, and immune responses. Key determinants of disease severity include antibody-dependent enhancement (ADE), cross-reactive T cells, anti-NS1 antibodies, autoimmunity, and genetic predisposition, with the NS1 protein and its antibodies strongly implicated in severe dengue. This review highlights recent advances in our understanding of how DENV impacts host immune responses at cellular, molecular, and genetic levels. We particularly focus on how the virus interacts with the host, alters immune responses, and escapes immune detection. These factors are crucial for disease progression and immune dysfunction. The host mounts both innate and adaptive immune responses involving interferon signalling, cytokine production, antigen presentation, and T-cell activation. However, DENV evades immunity by suppressing interferon pathways, disrupting antigen presentation, and leveraging antibody-dependent enhancement (ADE), leading to immune dysregulation, prolonged viremia, and severe dengue. Gaining insight into these host-pathogen interactions is essential for understanding dengue pathogenesis for designing safer and more effective therapeutics. Furthermore, integrating omics approaches with immune response models shows promise for identifying early, reliable markers that can predict disease severity and guide treatment. A deeper understanding of these processes will support the development of personalised treatment strategies and enhance preparedness for future dengue outbreaks.