Structures of vesicular stomatitis virus glycoprotein G alone and bound to a neutralizing antibody

Abstract

VSV G mediates viral entry via endocytosis. In the endosome, G undergoes a pH-dependent conformational change from pre- to post-fusion state, catalyzing membrane fusion. No complete structure of G has been reported so far. We present cryo-EM structures of G, isolated from virions using detergent, alone and in complex with the broadly neutralizing antibody 8G5F1 that binds all G conformations. The post-fusion structure reveals a novel rearrangement of the C-terminal part of the G ectodomain, showing that it undergoes a conformational rearrangement and stabilizes the post-fusion trimer by nesting into a groove between adjacent fusion domains. Structures of G-Fab complex show that the epitope belongs to a conserved antigenic site, explaining the broad neutralization capacity of the antibody. This work provides insights into the molecular basis of VSV G mediated fusion and antibody recognition, with potential implications for vaccine development, oncolytic virotherapy.