Dengue virus and West Nile virus envelope protein domain III (EDIII)

The envelope (E) protein is the primary surface protein of flaviviruses, including Dengue virus (DENV) and West Nile virus (WNV) [The Native Antigen Company, 2019]. It is organized into three distinct domains: EDI, EDII, and EDIII [The Native Antigen Company, 2019]. Domain III (EDIII) is an immunoglobulin-like fold located at the C-terminus of the E protein ectodomain and is the primary region responsible for host cell receptor binding and viral attachment [The Native Antigen Company, 2019; USK, 2022]. Because it contains the most potent epitopes for virus-specific neutralizing antibodies, EDIII is a critical target for the development of subunit vaccines and therapeutic monoclonal antibodies [NIH, 2022; ASM, 2023]. Targeting EDIII aims to block the initial interaction between the virus and the host cell, thereby preventing infection [The Native Antigen Company, 2019]. However, a major challenge in targeting this domain is the risk of antibody-dependent enhancement (ADE), where sub-neutralizing or cross-reactive antibodies facilitate viral entry into Fc-receptor-bearing cells, potentially leading to more severe disease manifestations like Dengue Hemorrhagic Fever [MDPI, 2023; USK, 2022].

Other names

Envelope protein domain IIIE-DIIIDIIIDomain III of the envelope proteinReceptor-binding domain of the E protein

Neutralization of viral infectivity by blocking host cell receptor binding and preventing viral attachment and entry [The Native Antigen Company, 2019; USK, 2022].