Structural basis for HCMV Pentamer receptor recognition and antibody neutralization.

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State: Public
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License: CC BY-NC 4.0
Serval ID
serval:BIB_9AD2F453F4AF
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Structural basis for HCMV Pentamer receptor recognition and antibody neutralization.
Journal
Science advances
Author(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., Payandeh J., Ciferri C.
ISSN
2375-2548 (Electronic)
ISSN-L
2375-2548
Publication state
Published
Issued date
11/03/2022
Peer-reviewed
Oui
Volume
8
Number
10
Pages
eabm2536
Language
english
Notes
Publication types: Journal Article
Publication Status: ppublish
Abstract
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.
Keywords
Multidisciplinary
Pubmed
Web of science
Open Access
Yes
Funding(s)
Swiss National Science Foundation / Projects / 310030_204679
Create date
15/03/2022 10:42
Last modification date
11/06/2022 6:35
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