Zika virus envelope glycoprotein (E protein) (ZIKV-E or E protein)

The Zika virus envelope glycoprotein (ZIKV-E) is a ~500 amino acid surface protein responsible for viral attachment to host cells and subsequent membrane fusion during viral entry. As the major structural component of the viral surface, the E protein assembles into 90 dimers forming an icosahedral shell containing 180 copies of the glycoprotein. The protein consists of four domains: three extracellular domains (I, II, and III) that constitute the β-strand surface portion and a transmembrane stem domain that anchors the protein in the lipid bilayer. The ZIKV-E protein is distinguished from other flaviviruses by a single N-linked glycosylation site at asparagine 154 (Asn154), which protrudes from the surface on a relatively long "150 loop" and may function as an attachment site for host cell receptors and lectins. This glycosylation site represents a major structural difference compared to dengue virus, which has two glycosylation sites. The protein also contains a unique positively charged patch adjacent to the fusion loop that may influence host cell attachment. As a primary target of neutralizing antibodies and a critical determinant of viral pathogenesis, the ZIKV-E protein has been extensively studied for vaccine and therapeutic development. Structural variations in the E protein, particularly deletions in the glycan loop region, have been associated with enhanced neurovirulence and severe congenital abnormalities in neonatal infection models.

Other names

Envelope proteinFlavivirus envelope glycoproteinSurface glycoprotein EViral envelope glycoprotein

Neutralizing antibodies target the fusion loop epitope, leading to cross-linking of E protein dimers which prevents conformational changes required for membrane fusion. Antibodies also bind to conserved epitopes spanning multiple E protein domains.