Two point mutations in protocadherin-1 disrupt hantavirus recognition and afford protection against lethal infection.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
24 07 2023
24 07 2023
Historique:
received:
04
04
2023
accepted:
06
07
2023
medline:
26
7
2023
pubmed:
25
7
2023
entrez:
24
7
2023
Statut:
epublish
Résumé
Andes virus (ANDV) and Sin Nombre virus (SNV) are the etiologic agents of severe hantavirus cardiopulmonary syndrome (HCPS) in the Americas for which no FDA-approved countermeasures are available. Protocadherin-1 (PCDH1), a cadherin-superfamily protein recently identified as a critical host factor for ANDV and SNV, represents a new antiviral target; however, its precise role remains to be elucidated. Here, we use computational and experimental approaches to delineate the binding surface of the hantavirus glycoprotein complex on PCDH1's first extracellular cadherin repeat domain. Strikingly, a single amino acid residue in this PCDH1 surface influences the host species-specificity of SNV glycoprotein-PCDH1 interaction and cell entry. Mutation of this and a neighboring residue substantially protects Syrian hamsters from pulmonary disease and death caused by ANDV. We conclude that PCDH1 is a bona fide entry receptor for ANDV and SNV whose direct interaction with hantavirus glycoproteins could be targeted to develop new interventions against HCPS.
Identifiants
pubmed: 37488123
doi: 10.1038/s41467-023-40126-y
pii: 10.1038/s41467-023-40126-y
pmc: PMC10366084
doi:
Substances chimiques
Protocadherins
0
Cadherins
0
Banques de données
figshare
['10.6084/m9.figshare.23401916.v1', '10.6084/m9.figshare.23398358', '10.6084/m9.figshare.23469236']
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
4454Subventions
Organisme : NIAID NIH HHS
ID : R01 AI132633
Pays : United States
Commentaires et corrections
Type : ErratumIn
Informations de copyright
© 2023. The Author(s).
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