Lassa virus glycoprotein precursor (GPC) (LASV GPC)

The Lassa virus glycoprotein precursor (GPC) is the primary surface protein of the Lassa virus (LASV), which causes Lassa fever, a severe hemorrhagic disease endemic to West Africa (UniProt P08669). GPC is synthesized as a precursor that is cleaved by the host protease SKI-1/S1P into three essential components: the stable signal peptide (SSP), the receptor-binding subunit (GP1), and the membrane-fusion subunit (GP2) (Hastie et al., 2017). These subunits assemble into a metastable trimeric spike on the viral envelope, which is responsible for mediating viral entry into host cells by binding to receptors such as alpha-dystroglycan and lysosome-associated membrane protein 1 (LAMP1) (Robinson et al., 2016). Because it is the only protein exposed on the virion surface, GPC is the critical target for neutralizing antibodies and vaccine design. Therapeutic strategies currently focus on monoclonal antibodies, such as the Arevirumab cocktail, which bind to the GPC complex to inhibit viral attachment or fusion (Cross et al., 2019). However, the high sequence variability among different LASV lineages and the presence of a dense glycan shield present significant challenges for developing broadly effective therapeutics targeting this molecule.

Other names

Lassa virus GPCLassa virus envelope glycoproteinGP1/GP2 complexLassa virus GP antigenLassa virus glycoprotein

Neutralization of viral infection by binding to the GPC trimer, thereby blocking receptor binding (alpha-dystroglycan or LAMP1) or preventing the pH-dependent conformational changes required for membrane fusion.