A neutralizing antibody prevents post-fusion transition of measles virus fusion protein
Résumé
Measles virus (MeV) presents a public health threat that is escalating as vaccine coverage in the general population declines and as populations of immunocompromised individuals, who cannot be vaccinated, increase. There are no approved therapeutics for MeV. Neutralizing antibodies targeting viral fusion are one potential therapeutic approach but have not yet been structurally characterized or advanced to clinical use. We present cryo-EM structures of pre-fusion F alone (2.1-Å resolution), F complexed with a fusioninhibitory peptide (2.3 Å), F complexed with the neutralizing and protective antibody mAb 77 (2.6 Å), and an additional structure of post-fusion F (2.7 Å). In vitro assays and examination of additional EM classes show mAb 77 binds pre-fusion F, arrests F in an intermediate state and prevents transition to the post-fusion conformation. These structures shed light on antibody-mediated neutralization that involves arrest of fusion proteins in an intermediate state.
Domaines
Virologie| Origine | Fichiers produits par l'(les) auteur(s) |
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