Lassa virus glycoprotein: stopping a moving target

• Published in: Current opinion in virology 2018-08, Vol.31, p.52-58
• Main Authors: Hastie, Kathryn M, Saphire, Erica Ollmann
• Format: Article
• Language: English
• Subjects: Arenavirus - metabolism; Epitopes - immunology; Glycoproteins - chemistry; Glycoproteins - metabolism; Humans; Lassa virus - chemistry; Lassa virus - metabolism; Protein Binding; Protein Structure, Tertiary; Viral Envelope Proteins - metabolism; Virus Internalization
• ISSN: 1879-6257; 1879-6265
• DOI: 10.1016/j.coviro.2018.05.002

•The Lassa virus GPC trimer has a unique architecture amongst class I viral GPCs.•Multiple conformations of both Lassa virus subunits exist.•Quaternary epitope antibodies are the most potent in Lassa virus neutralization.•Features specific to the arenavirus GPC can guide vaccine design. The structure of a prefusion arenavirus GPC was enigmatic for many years, owing to the metastable and non-covalent nature of the association between the receptor binding and fusion subunits. Recent engineering efforts to stabilize the glycoprotein of the Old World arenavirus Lassa in a native, yet cleaved state, allowed the first structure of any arenavirus prefusion GPC trimer to be determined. Comparison of this structure with the structures of other arenavirus glycoprotein subunits reveals surprising findings: that the receptor binding subunit, GP1, of Lassa virus is conformationally labile, while the GP1 subunit of New World arenaviruses is not, and that the arenavirus GPC adopts a trimeric state unlike other glycoproteins with similar fusion machinery. Structural analysis, combined with recent biochemical data regarding antibody epitopes and receptor binding requirements, provides a basis for rational vaccine design.