Lassa fever is a severe, sometimes fatal, hemorrhagic disease. It is caused by the Lassa virus, a single-stranded RNA virus in the arenavirus family. There is no available vaccine. The only antigen on the viral surface is the glycoprotein GPC that engages host cell receptors. Hastie et al. report the high-resolution structure of the trimeric ectodomain of GPC bound to a neutralizing antibody from a human survivor of the disease. The structure gives insight into viral entry mechanisms and antibody neutralization and provides a template for vaccine design.
Science, this issue p. 923
The arenavirus Lassa causes severe hemorrhagic fever and a significant disease burden in West Africa every year. The glycoprotein, GPC, is the sole antigen expressed on the viral surface and the critical target for antibody-mediated neutralization. Here we present the crystal structure of the trimeric, prefusion ectodomain of Lassa GP bound to a neutralizing antibody from a human survivor at 3.2-angstrom resolution. The antibody extensively anchors two monomers together at the base of the trimer, and biochemical analysis suggests that it neutralizes by inhibiting conformational changes required for entry. This work illuminates pH-driven conformational changes in both receptor-binding and fusion subunits of Lassa virus, illustrates the unique assembly of the arenavirus glycoprotein spike, and provides a much-needed template for vaccine design against these threats to global health.