Flavivirus envelope protein E (E protein)

Flavivirus envelope protein E is the principal surface glycoprotein of flaviviruses (such as dengue, Zika, West Nile, Japanese encephalitis, and yellow fever viruses), mediating both receptor binding and fusion between viral and host cellular membranes during infection[1][3][5]. The protein is composed of three structural domains (EDI, EDII, EDIII) linked by flexible hinges, allowing dramatic conformational changes critical for the viral entry process[1][5][7]. It exists as antiparallel homodimers on the virion surface and transitions to a trimeric state at acidic pH in endosomes, exposing the highly conserved fusion peptide and facilitating membrane fusion[1][3][5]. The E protein is a major target of neutralizing antibodies, and several epitopes (notably in the fusion loop and domain III) underpin serodiagnostic and vaccine strategies[2][4]. Therapeutic targeting of E protein must carefully weigh the risk of ADE, which can enhance infection if subneutralizing antibodies promote viral uptake into Fc-receptor–bearing cells[2][7]. The protein’s structure, antigenic regions, and mechanisms of conformational rearrangement are well characterized and are central to flavivirus biology, immunopathogenesis, and antiviral development[1][3][5][7].

Other names

Envelope glycoprotein EE glycoproteinFlavivirus E protein

Inhibition of virus-cell membrane fusion Neutralization by blocking receptor attachment or conformational changes