Lassa virus glycoprotein precursor complex (GPC)

The Lassa virus glycoprotein precursor complex (GPC) is the sole protein displayed on the viral surface and serves as the critical mediator of viral entry into host cells. Synthesized as a 76-kDa precursor, GPC is proteolytically processed in the endoplasmic reticulum by the host cell protease SKI-1/S1P into three mature subunits: glycoprotein 1 (GP1), glycoprotein 2 (GP2), and a stable signal peptide (SSP). The receptor-binding subunit GP1 initially engages α-dystroglycan on the cell surface, while GP2 mediates membrane fusion through a class I fusion mechanism involving two distinct fusion peptides and heptad repeat regions. Upon acidic pH exposure in late endosomes, GP1 undergoes an unusual receptor switch to bind LAMP1, triggering conformational changes that expose GP2's fusion peptides and enable formation of a six-helix bundle that drives membrane fusion. The mature GPC exists as a trimer of tripartite monomers on the virion surface and is heavily glycosylated with 11 N-linked glycosylation sites per monomer, conferring approximately 30% of the complex's total mass as carbohydrate and enabling evasion of neutralizing antibody responses. As the only surface antigen of Lassa virus, GPC is the primary target for vaccine development and antibody-based therapeutics against Lassa fever, a lethal hemorrhagic fever endemic to West Africa.

Other names

Lassa virus glycoprotein precursorGP-CSurface glycoprotein precursorGlycoprotein complex

Antibody-mediated neutralization by binding to epitopes on the GPC surface Potential small molecule inhibitors targeting the fusion peptide or receptor-binding domains (under investigation)