Structural basis for HCMV Pentamer receptor recognition and antibody neutralization.

Détails

Ressource 1Télécharger: sciadv.abm2536 (1).pdf (4271.94 [Ko])
Etat: Public
Version: de l'auteur⸱e
Licence: CC BY-NC 4.0
ID Serval
serval:BIB_9AD2F453F4AF
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Structural basis for HCMV Pentamer receptor recognition and antibody neutralization.
Périodique
Science advances
Auteur⸱e⸱s
Kschonsak M., Johnson M.C., Schelling R., Green E.M., Rougé L., Ho H., Patel N., Kilic C., Kraft E., Arthur C.P., Rohou A.L., Comps-Agrar L., Martinez-Martin N., Perez L. (co-dernier), Payandeh J. (co-dernier), Ciferri C. (co-dernier)
ISSN
2375-2548 (Electronic)
ISSN-L
2375-2548
Statut éditorial
Publié
Date de publication
11/03/2022
Peer-reviewed
Oui
Volume
8
Numéro
10
Pages
eabm2536
Langue
anglais
Notes
Publication types: Journal Article
Publication Status: ppublish
Résumé
Human cytomegalovirus (HCMV) represents the viral leading cause of congenital birth defects and uses the gH/gL/UL128-130-131A complex (Pentamer) to enter different cell types, including epithelial and endothelial cells. Upon infection, Pentamer elicits the most potent neutralizing response against HCMV, representing a key vaccine candidate. Despite its relevance, the structural basis for Pentamer receptor recognition and antibody neutralization is largely unknown. Here, we determine the structures of Pentamer bound to neuropilin 2 (NRP2) and a set of potent neutralizing antibodies against HCMV. Moreover, we identify thrombomodulin (THBD) as a functional HCMV receptor and determine the structures of the Pentamer-THBD complex. Unexpectedly, both NRP2 and THBD also promote dimerization of Pentamer. Our results provide a framework for understanding HCMV receptor engagement, cell entry, antibody neutralization, and outline strategies for antiviral therapies against HCMV.
Mots-clé
Multidisciplinary
Pubmed
Web of science
Open Access
Oui
Financement(s)
Fonds national suisse / Projets / 310030_204679
Création de la notice
15/03/2022 9:42
Dernière modification de la notice
21/11/2022 8:23
Données d'usage