Flavivirus envelope glycoprotein (E protein) (E protein)

The Flavivirus envelope (E) glycoprotein is the principal surface component of viruses within the Flaviviridae family, including Dengue, Zika, and West Nile viruses (Pierson & Diamond, 2020, Nature Microbiology). It is a class II viral fusion protein that mediates the critical initial steps of infection, including attachment to host cell receptors and subsequent fusion between the viral and endosomal membranes (Rey et al., 1995, Nature). Structurally, the E protein is organized as homodimers on the surface of mature virions, which reorganize into trimers upon exposure to the acidic environment of the endosome to trigger the fusion process (Modis et al., 2004, Nature). Because it is the primary target for neutralizing antibodies, the E protein is the central focus for the development of vaccines and therapeutic monoclonal antibodies (Heinz & Stiasny, 2012, Vaccine). However, a significant challenge in targeting this protein is antibody-dependent enhancement (ADE), where non-neutralizing or sub-neutralizing antibodies can facilitate viral entry into immune cells via Fc receptors, potentially worsening the disease (Katzelnick et al., 2017, Science). This phenomenon is particularly relevant for Dengue virus, where cross-reactive antibodies from a previous infection with a different serotype can lead to severe dengue hemorrhagic fever.

Other names

Envelope proteinE glycoproteinFlavivirus E proteinViral envelope protein

Neutralization of viral particles by blocking receptor attachment or inhibiting the pH-dependent conformational change required for membrane fusion (Heinz & Stiasny, 2012, Vaccine).