Dengue virus envelope protein domain III (EDIII)

Dengue virus envelope protein domain III (EDIII) is the C-terminal domain of the major structural glycoprotein (E protein) found on the surface of the Dengue virus (DENV) [1, 9]. It adopts a stable immunoglobulin-like fold and is primarily responsible for recognizing and binding to host cell receptors, thereby facilitating viral attachment and entry via receptor-mediated endocytosis [6, 10, 20]. EDIII is a critical target for the host's immune system, as it contains potent epitopes that elicit serotype-specific neutralizing antibodies [1, 2, 12]. Because of its role in infection and its ability to induce protective immunity, EDIII is a major focus for the development of subunit vaccines and therapeutic monoclonal antibodies, such as Visivumab (VIS513) [18, 23, 24, 32]. However, a significant challenge in targeting EDIII is the risk of antibody-dependent enhancement (ADE), where sub-neutralizing or cross-reactive antibodies can paradoxically increase viral uptake into Fc-receptor-bearing cells, potentially leading to severe disease forms like Dengue hemorrhagic fever [3, 4, 7, 13]. Additionally, recent research has implicated EDIII in the activation of innate inflammatory pathways, including the NLRP3 inflammasome and NETosis, which contribute to the cytokine storm observed in severe Dengue cases [5, 14].

Other names

EDIIIE-DIIIDomain III of the envelope proteinDIIIEnvelope protein domain 3

Neutralization of the virus by blocking host cell receptor binding and inhibiting viral entry and membrane fusion [1, 6, 10, 29].