Lassa virus glycoprotein complex precursor (LASV GPC precursor)

The Lassa virus glycoprotein complex precursor is translated as a single polypeptide (pre-GPC or pre-GP-C) in infected cells, which is then proteolytically cleaved into three subunits: glycoprotein 1 (GP1), glycoprotein 2 (GP2), and a stable signal peptide (SSP). The mature GPC trimer forms the viral spike present on the surface of Lassa virus particles and is responsible for viral attachment and membrane fusion during the infection process. GP1 subunit binds to the host cell receptor α-dystroglycan and, after endocytosis and trafficking to the late endosome, switches to the LAMP1 receptor, a process unique to Lassa virus. The glycoprotein complex is densely glycosylated, forming a glycan shield that helps the virus evade the humoral immune response. The GPC precursor and its processed forms are the main targets for therapeutic monoclonal antibodies and vaccine candidates, as neutralizing antibodies directed against different epitopes on the complex can block viral entry and provide protection. Structural insights have facilitated the design of stabilized GPC trimers for vaccine approaches. The target’s sequence and structure are highly lineage-dependent, and immune escape variants may arise, presenting challenges for the development of broadly effective therapies and vaccines.

Other names

Lassa virus glycoprotein precursorLASV GPC precursorLassa viral spike precursorpre-GPCpre-GP-C

Neutralization/blocking of receptor binding (dystroglycan and LAMP1) Inhibition of membrane fusion and virus entry into host cells