Dengue virus and host immune system (DENV-Host Immune Interaction)

The interaction between the Dengue virus (DENV) and the host immune system is a complex biological process that determines the clinical progression from mild dengue fever to severe dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS) [1, 2, 20]. DENV, a positive-sense RNA flavivirus with four distinct serotypes, utilizes its non-structural (NS) proteins to subvert host defenses; for example, NS5 inhibits type I interferon signaling by targeting STAT2 for degradation, while NS1 acts as a multitasking toxin that disrupts endothelial barriers and evades the complement system [5, 6, 10, 15]. A critical and paradoxical feature of this interaction is antibody-dependent enhancement (ADE), where pre-existing, non-neutralizing antibodies from a previous infection facilitate viral entry into Fc gamma receptor-bearing immune cells during a secondary infection with a different serotype [8, 13, 14]. This leads to massive viral replication and a "cytokine storm" involving TNF-alpha, IL-6, and IL-10, which triggers systemic vascular leakage and coagulopathy [1, 16, 20]. Therapeutic interventions focus on achieving balanced tetravalent immunity through vaccines like Dengvaxia and Qdenga, or developing small molecules that target viral enzymes such as the NS3 protease/helicase and NS5 polymerase to halt replication and immune evasion [1, 6, 9, 12].

Other names

DENV-host interactionDengue virus immune evasionDengue immunopathogenesisDengue virus-host crosstalk

Active immunization via tetravalent vaccines, inhibition of viral enzymes (NS3 protease/helicase, NS5 polymerase), and modulation of host factors to prevent antibody-dependent enhancement and cytokine storms.