Two point mutations in protocadherin-1 disrupt hantavirus recognition and afford protection against lethal infection
© 2023. The Author(s)..
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.
| Errataetall: |
ErratumIn: Nat Commun. 2023 Sep 22;14(1):5924. - PMID 37739957 |
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| Medienart: |
E-Artikel |
| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:14 |
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| Enthalten in: |
Nature communications - 14(2023), 1 vom: 24. Juli, Seite 4454 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Slough, Megan M [VerfasserIn] |
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| Links: |
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| Themen: |
Cadherins |
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| Anmerkungen: |
Date Completed 26.07.2023 Date Revised 12.02.2024 published: Electronic figshare: 10.6084/m9.figshare.23401916.v1, 10.6084/m9.figshare.23398358, 10.6084/m9.figshare.23469236 ErratumIn: Nat Commun. 2023 Sep 22;14(1):5924. - PMID 37739957 Citation Status MEDLINE |
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| doi: |
10.1038/s41467-023-40126-y |
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| 245 | 1 | 0 | |a Two point mutations in protocadherin-1 disrupt hantavirus recognition and afford protection against lethal infection |
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| 500 | |a ErratumIn: Nat Commun. 2023 Sep 22;14(1):5924. - PMID 37739957 | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2023. The Author(s). | ||
| 520 | |a 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 | ||
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| 700 | 1 | |a Lasso, Gorka |e verfasserin |4 aut | |
| 700 | 1 | |a Kuehne, Ana I |e verfasserin |4 aut | |
| 700 | 1 | |a Monticelli, Stephanie R |e verfasserin |4 aut | |
| 700 | 1 | |a Bakken, Russell R |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Yanan |e verfasserin |4 aut | |
| 700 | 1 | |a Ghosh, Agnidipta |e verfasserin |4 aut | |
| 700 | 1 | |a Moreau, Alicia M |e verfasserin |4 aut | |
| 700 | 1 | |a Zeng, Xiankun |e verfasserin |4 aut | |
| 700 | 1 | |a Rey, Félix A |e verfasserin |4 aut | |
| 700 | 1 | |a Guardado-Calvo, Pablo |e verfasserin |4 aut | |
| 700 | 1 | |a Almo, Steven C |e verfasserin |4 aut | |
| 700 | 1 | |a Dye, John M |e verfasserin |4 aut | |
| 700 | 1 | |a Jangra, Rohit K |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Zhongde |e verfasserin |4 aut | |
| 700 | 1 | |a Chandran, Kartik |e verfasserin |4 aut | |
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