Chikungunya virus E2 envelope protein (CHIKV E2)

The Chikungunya virus E2 envelope protein is a type I transmembrane glycoprotein that serves as the primary attachment factor for the virus to host cells. It forms a heterodimeric complex with the E1 fusion protein, which is arranged into 80 trimeric spikes on the surface of the virion (UniProt, 2024). The E2 protein is responsible for binding to host cell receptors, most notably the Matrix Remodeling Associated 8 (Mxra8) protein, which facilitates viral entry into various cell types including fibroblasts and osteoblasts (Zhang et al., 2019). Upon endocytosis, the low-pH environment of the endosome induces a dissociation of the E2-E1 heterodimer, allowing E1 to mediate the fusion of viral and host membranes (Voss et al., 2010). Because of its exposed position on the viral surface, E2 is the principal target for the host's neutralizing antibody response and a primary focus for vaccine design, such as the live-attenuated vaccine Ixchiq (FDA, 2023). Therapeutic strategies targeting E2 include monoclonal antibodies that sterically hinder receptor binding or prevent the conformational changes required for fusion (Fox et al., 2015). These antibodies, such as CHK-152, have demonstrated high potency in neutralizing the virus by binding to specific epitopes on the E2 A and B domains (Pal et al., 2013). Understanding the structural biology of E2 is essential for addressing Chikungunya fever, a disease characterized by debilitating joint pain and fever.

Other names

E2 glycoproteinEnvelope glycoprotein E2Spike protein E2CHIKV E2 protein

Neutralization of viral infectivity by blocking attachment to host cell receptors (such as Mxra8) and preventing the pH-dependent conformational changes required for E1-mediated membrane fusion (Zhang et al., 2019; Fox et al., 2015).