Envelope glycoprotein E (E protein) (E protein)

The Envelope glycoprotein E is a primary structural protein and a critical therapeutic target found in several major human pathogens, most notably within the Flaviviridae family (e.g., Dengue, Zika, West Nile, and Yellow Fever viruses) and the Herpesviridae family (specifically Varicella-zoster virus, VZV). In Flaviviruses, the E protein is a Class II viral fusion protein that mediates host cell receptor binding and pH-dependent membrane fusion within the endosome, facilitating viral entry [UniProt P17758; Nature Reviews Microbiology, 10.1038/nrmicro3010]. In VZV, the glycoprotein E (gE) is the most abundant viral surface protein and is essential for viral replication, assembly, and cell-to-cell spread [UniProt P09299; Journal of Virology, 10.1128/JVI.01733-17]. As the most exposed protein on the virion surface, Envelope glycoprotein E is the principal target for neutralizing antibodies and the central component of several highly effective vaccines. For instance, the Shingrix vaccine utilizes a recombinant version of VZV gE to prevent shingles, while Dengue vaccines like Dengvaxia and Qdenga target the E proteins of the four Dengue serotypes [CDC, Shingrix; WHO, Dengue Vaccines]. Therapeutic challenges include the risk of antibody-dependent enhancement (ADE) in Dengue infections, where sub-neutralizing antibodies against the E protein can paradoxically facilitate viral entry into immune cells, and the high degree of structural variability among different virus strains [Science, 10.1126/science.1259357].

Other names

Glycoprotein EgEEnvelope protein EViral envelope protein EMajor envelope glycoprotein

Neutralization of viral entry by blocking receptor binding or inhibiting pH-dependent membrane fusion; induction of protective humoral and cellular immune responses.