The Role of Natural Killer (NK) Cells in Dengue Virus Infection: A Narrative Review

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Background and Aims: In the innate immune response, natural Killer (NK) cells have a significant role in protection against viral infections, including the Dengue virus (DENV). NK cells identify and eliminate virus‐infected cells through diverse mechanisms, such as cytokine production, cytolytic activity, and antibody‐dependent cellular cytotoxicity (ADCC), thereby contributing to reducing viremia and regulating adaptive immunity in the context of DENV. This review summarises the biological mechanisms of NK‐cell‐mediated immune response against DENV, describes the viral evasion of NK immune protection and explores the insights for the immunotherapeutic approaches and drug development. Methods: To conduct this narrative review, we searched the literature on NK cell activation, receptor expression, cytokine responses, virus evasion strategies, and experimental or emerging therapeutic approaches in DENV. Results: NK cells recognise DENV through the interaction of inhibitory receptors along with the human leukocyte antigen (HLA) class I molecules, which in turn strengthens the ADCC response. DENV can apply virus evasion strategies for modulating NK cell‐mediated immunity and reducing the antiviral effect. In addition, impaired and exhausted NK cell phenotypes are associated with the progression and severity of dengue syndromes. Conclusion: NK cells play a double‐edged sword in protective response and immune function during DENV. A deeper understanding of their NK cell mechanism, subset heterogeneity, functional response, and evasion strategies governs key insights for vaccines and therapeutic strategies that prompt antiviral immune response.

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