Zika virus envelope protein domain III (ZIKV EDIII)

The Zika virus envelope protein domain III (ZIKV EDIII) is a structural domain of the viral envelope glycoprotein E, which covers the virus surface in 180 copies arranged in dimers. It forms a barrel-like immunoglobulin domain composed of antiparallel β-sheets and serves critical roles in receptor binding, host cell entry, and membrane fusion during infection. EDIII contains potent antigenic epitopes, particularly on the lateral ridge, that elicit neutralizing antibodies from the VH3-23/VK1-5 class, which bind with high affinity (picomolar to low nanomolar KD) after somatic hypermutation, especially in the light-chain variable domain. These antibodies prevent Zika virus (ZIKV) infection but show cross-reactivity with dengue virus (DENV1-4) and West Nile virus (WNV), raising concerns for antibody-dependent enhancement (ADE) that could worsen flavivirus disease severity. As a vaccine immunogen, recombinant ZIKV EDIII induces protective, type-specific neutralizing responses without ADE risks associated with full E protein. Structural studies reveal key interactions like the EK motif (E393-K394) essential for high-affinity binding and neutralization. Targeting EDIII supports diagnostic applications and immunotherapies, though no approved drugs exist.

Other names

Zika virus E protein domain IIIZIKV envelope domain IIIEDIII

Neutralizing antibody binding to lateral ridge epitope, preventing viral entry; Antibody-dependent enhancement (ADE) via cross-reactive binding to other flaviviruses