Mechanistic basis for potent neutralization of Sin Nombre hantavirus by a human monoclonal antibody
© 2023. The Author(s)..
Rodent-borne hantaviruses are prevalent worldwide and upon spillover to human populations, cause severe disease for which no specific treatment is available. A potent antibody response is key for recovery from hantavirus infection. Here we study a highly neutralizing human monoclonal antibody, termed SNV-42, which was derived from a memory B cell isolated from an individual with previous Sin Nombre virus (SNV) infection. Crystallographic analysis demonstrates that SNV-42 targets the Gn subcomponent of the tetrameric (Gn-Gc)4 glycoprotein assembly that is relevant for viral entry. Integration of our 1.8 Å structure with the (Gn-Gc)4 ultrastructure arrangement indicates that SNV-42 targets the membrane-distal region of the virus envelope. Comparison of the SNV-42 paratope encoding variable genes with inferred germline gene segments reveals high sequence conservation, suggesting that germline-encoded antibodies inhibit SNV. Furthermore, mechanistic assays reveal that SNV-42 interferes with both receptor recognition and fusion during host-cell entry. This work provides a molecular-level blueprint for understanding the human neutralizing antibody response to hantavirus infection.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:8 |
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| Enthalten in: |
Nature microbiology - 8(2023), 7 vom: 15. Juli, Seite 1293-1303 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Stass, Robert [VerfasserIn] |
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| Links: |
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| Themen: |
Antibodies, Monoclonal |
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| Anmerkungen: |
Date Completed 07.07.2023 Date Revised 19.07.2023 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1038/s41564-023-01413-y |
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| funding: |
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| Förderinstitution / Projekttitel: |
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NLM358237017 |
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| 520 | |a © 2023. The Author(s). | ||
| 520 | |a Rodent-borne hantaviruses are prevalent worldwide and upon spillover to human populations, cause severe disease for which no specific treatment is available. A potent antibody response is key for recovery from hantavirus infection. Here we study a highly neutralizing human monoclonal antibody, termed SNV-42, which was derived from a memory B cell isolated from an individual with previous Sin Nombre virus (SNV) infection. Crystallographic analysis demonstrates that SNV-42 targets the Gn subcomponent of the tetrameric (Gn-Gc)4 glycoprotein assembly that is relevant for viral entry. Integration of our 1.8 Å structure with the (Gn-Gc)4 ultrastructure arrangement indicates that SNV-42 targets the membrane-distal region of the virus envelope. Comparison of the SNV-42 paratope encoding variable genes with inferred germline gene segments reveals high sequence conservation, suggesting that germline-encoded antibodies inhibit SNV. Furthermore, mechanistic assays reveal that SNV-42 interferes with both receptor recognition and fusion during host-cell entry. This work provides a molecular-level blueprint for understanding the human neutralizing antibody response to hantavirus infection | ||
| 650 | 4 | |a Journal Article | |
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| 700 | 1 | |a Engdahl, Taylor B |e verfasserin |4 aut | |
| 700 | 1 | |a Chapman, Nathaniel S |e verfasserin |4 aut | |
| 700 | 1 | |a Wolters, Rachael M |e verfasserin |4 aut | |
| 700 | 1 | |a Handal, Laura S |e verfasserin |4 aut | |
| 700 | 1 | |a Diaz, Summer M |e verfasserin |4 aut | |
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| 700 | 1 | |a Bowden, Thomas A |e verfasserin |4 aut | |
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