Variations in Core Packing of GP2 from Old World Mammarenaviruses in their Post-Fusion Conformations Affect Membrane-Fusion Efficiencies.

Lassa virus (LASV) is a notorious human pathogen in West Africa. Its class I trimeric spike complex displays a distinct architecture， and its cell entry mechanism involves unique attributes not shared by other related viruses. We determined the crystal structure of the GP2 fusion glycoprotein from the spike complex of LASV (GP2) in its post-fusion conformation. GP2 adopts a canonical helical bundle configuration similarly to other viruses in its family. The core packing of GP2， however， is more organized compared to GP2 from other viruses reducing the formation of internal hydrophobic cavities. We demonstrate a link between the formation of such unfavorable hydrophobic cavities and the efficiencies of membrane fusion and cell entry. Our study suggests that LASV has evolved a more efficient membrane fusogen compared to other viruses from its family by optimizing the post-fusion configuration of its GP2 module.