In situ insights into antibody-mediated neutralization of a pre-fusion Junin virus glycoprotein complex.

ABSTRACT: A transmembrane glycoprotein complex (GPC) decorates the Junin mammarenavirus (JUNV) that causes New World hemorrhagic fevers. We leveraged single-particle cryoelectron microscopy (cryo-EM) to image the full-length JUNV GPC directly on pseudotyped virus (PV) membranes and bound by two JUNV-neutralizing antibodies: Candid#1 vaccine-elicited CR1-28 and J199, a potent therapeutic against Argentine hemorrhagic fever (AHF). The 3.8 Å resolution in situ structures of the antibody-neutralized, 3-fold symmetric JUNV GPC reveal its ectodomain architecture, signal peptide-bound transmembrane region, zinc-binding luminal domain, and post-translational modifications. JUNV-GPC sequence variants highlight the functional importance of the signal peptide transmembrane helix register for virus infection an

SUBMITTER: Taylor LJ 

PROVIDER: S-EPMC12450071 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature