Venezuelan equine encephalitis virus glycoprotein (VEEV GP)

The Venezuelan equine encephalitis virus (VEEV) glycoprotein complex, consisting of the E1 and E2 subunits, is the primary mediator of viral entry into host cells. The E2 protein facilitates initial attachment by binding to specific host receptors, most notably the Low-Density Lipoprotein Receptor Class A Domain Containing 3 (LDLRAD3) in humans (Ma et al., Nature 2020). Following endocytosis, the acidic environment of the endosome triggers a conformational change in the E1 protein, which acts as a class II fusion protein to merge the viral and host membranes (Voss et al., Nature 2010). Because it is the most exposed part of the virus, the glycoprotein is the principal target for the host immune response and the primary focus for vaccine candidates like TC-83 and V3526, as well as neutralizing monoclonal antibodies such as 1A4A-1 (Hunt et al., J. Virol. 2010). Targeting this complex is essential for preventing the rapid neuroinvasion and subsequent encephalitis characteristic of VEEV infection. Therapeutic strategies often aim to neutralize the virus by sterically hindering receptor binding or by stabilizing the prefusion state of the E1/E2 complex (UniProt P03316).

Other names

VEEV envelope proteinVEEV spike proteinE1/E2 glycoprotein complexVEEV E1 proteinVEEV E2 proteinAlphavirus glycoprotein

Neutralization of viral particles by blocking receptor binding (E2) or preventing pH-triggered membrane fusion (E1) within the host endosome.