Zika virus envelope protein domain III (EDIII) lateral ridge and DI-DIII linker region (ZIKV EDIII LR/linker)

The Zika virus envelope (E) protein domain III (EDIII) lateral ridge and the DI-DIII linker region constitute a critical antigenic site on the surface of the Zika virus (ZIKV) virion. The E protein is the primary protein involved in viral attachment and entry into host cells, with EDIII specifically implicated in binding to cellular receptors (Sapparapu et al., 2016, Nature). The lateral ridge (LR) of EDIII is a highly accessible epitope that elicits potent, ZIKV-specific neutralizing antibodies, distinguishing it from the more conserved EDI/II regions (Stettler et al., 2016, Science). These EDI/II regions often trigger cross-reactive antibodies that can lead to antibody-dependent enhancement (ADE) of infection, making EDIII a safer target for therapeutic intervention. The DI-DIII linker provides structural flexibility necessary for the conformational changes the E protein undergoes during the fusion process in the endosome (Hasan et al., 2017, Nature). Therapeutic strategies targeting this region, primarily through monoclonal antibodies like ZV-67 or ZV-48, aim to block viral attachment or prevent the structural transitions required for membrane fusion (Zhao et al., 2016, Cell). Because this region is relatively specific to Zika virus compared to other flaviviruses like Dengue, it is a primary focus for diagnostic development and vaccine design.

Other names

Zika virus EDIII lateral ridgeZIKV E-DIII LRZika virus E protein domain IIIZIKV DI-DIII linkerZika virus envelope protein domain III lateral ridge

Neutralization of viral entry by blocking receptor binding and inhibiting conformational changes required for membrane fusion.