Lassa Virus Cell Entry Reveals New Aspects of Virus-Host Cell Interaction

Abstract

Viral entry represents the first step of every viral infection and is a determinant for the host range and disease potential of a virus. Here, we review the latest developments on cell entry of the highly pathogenic Old World arenavirus Lassa virus, providing novel insights into the complex virus-host cell interaction of this important human pathogen. We will cover new discoveries on the molecular mechanisms of receptor recognition, endocytosis, and the use of late endosomal entry factors.

Keywords: Lassa fever; endocytosis; late endosome; receptor; viral entry.

FIG 1

Current model for receptor use, cell entry, and the late endosomal receptor switch of LASV (64, 65, 67). At the cell surface, LASV GP1 engages the O-linked matriglycan polysaccharides displayed by α-DG, followed by endocytosis via an unusual pathway related to macropinocytosis. Progressive acidification of late endosomes induces a structural change in LASV GP1, which dissociates from DG and adapts a low-pH conformation displaying a histidine triad. Protonation of residue H230 “locks” GP1 in the prefusion state, preventing premature fusion. Engagement of LAMP1 neutralizes the positive charge on H230 of GP1 and triggers efficient fusion with the limiting membrane of the late endosome/lysosome (for details, please see the text).