Lassa mammarenavirus glycoprotein complex (LASV GPC)

The Lassa mammarenavirus glycoprotein complex (GPC) is a trimeric class I fusion protein located on the viral envelope that is essential for the entry of Lassa virus (LASV) into host cells [1]. It is synthesized as a precursor polypeptide that undergoes proteolytic cleavage by cellular signal peptidase and the protease SKI-1/S1P into three non-covalently associated subunits: the stable signal peptide (SSP), the receptor-binding subunit (GP1), and the transmembrane fusion subunit (GP2) [2]. GP1 is responsible for host cell attachment, initially binding to alpha-dystroglycan and later switching to the endosomal receptor lysosome-associated membrane protein 1 (LAMP1) within the acidified endosome [3]. This low-pH environment triggers a massive conformational change in GP2, which inserts a fusion peptide into the host membrane to facilitate viral-cell membrane fusion [4]. As the only protein displayed on the surface of the virion, GPC is the primary target for the development of vaccines, neutralizing monoclonal antibodies, and small-molecule fusion inhibitors aimed at preventing Lassa fever [5]. [1] https://www.uniprot.org/uniprotkb/P08669/entry [2] https://pubmed.ncbi.nlm.nih.gov/28539537/ [3] https://pubmed.ncbi.nlm.nih.gov/24990431/ [4] https://pubmed.ncbi.nlm.nih.gov/30135571/ [5] https://pubmed.ncbi.nlm.nih.gov/29133451/

Other names

Lassa virus glycoprotein complexLASV GlycoproteinPre-glycoprotein polyprotein GP complexGPC

Inhibition of viral-cell membrane fusion, neutralization of viral attachment by blocking receptor binding sites on GP1, and stabilization of the pre-fusion conformation of the GP1/GP2 complex.