Structural basis for antibody-mediated neutralization of Lassa virus
The arenavirus Lassa causes severe hemorrhagic fever and a significant disease burden in West Africa every year. The glycoprotein, GPC, is the sole antigen expressed on the viral surface and the critical target for antibody-mediated neutralization. Here we present the crystal structure of the trimeric, prefusion ectodomain of Lassa GP bound to a neutralizing antibody from a human survivor at 3.2-angstrom resolution. The antibody extensively anchors two monomers together at the base of the trimer, and biochemical analysis suggests that it neutralizes by inhibiting conformational changes required for entry. This work illuminates pH-driven conformational changes in both receptor-binding and fusion subunits of Lassa virus, illustrates the unique assembly of the arenavirus glycoprotein spike, and provides a much-needed template for vaccine design against these threats to global health..
| Medienart: |
Artikel |
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| Erscheinungsjahr: |
2017 |
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| Erschienen: |
2017 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:356 |
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| Enthalten in: |
Science - 356(2017), 6341, Seite 923 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Hastie, Kathryn M [VerfasserIn] |
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| Links: |
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| doi: |
10.1126/science.aam7260 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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OLC1994538074 |
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| 245 | 1 | 0 | |a Structural basis for antibody-mediated neutralization of Lassa virus |
| 264 | 1 | |c 2017 | |
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| 520 | |a The arenavirus Lassa causes severe hemorrhagic fever and a significant disease burden in West Africa every year. The glycoprotein, GPC, is the sole antigen expressed on the viral surface and the critical target for antibody-mediated neutralization. Here we present the crystal structure of the trimeric, prefusion ectodomain of Lassa GP bound to a neutralizing antibody from a human survivor at 3.2-angstrom resolution. The antibody extensively anchors two monomers together at the base of the trimer, and biochemical analysis suggests that it neutralizes by inhibiting conformational changes required for entry. This work illuminates pH-driven conformational changes in both receptor-binding and fusion subunits of Lassa virus, illustrates the unique assembly of the arenavirus glycoprotein spike, and provides a much-needed template for vaccine design against these threats to global health. | ||
| 540 | |a Nutzungsrecht: © COPYRIGHT 2017 American Association for the Advancement of Science | ||
| 650 | 4 | |a Antibodies | |
| 650 | 4 | |a Crystals | |
| 650 | 4 | |a Viral antibodies | |
| 650 | 4 | |a Analysis | |
| 650 | 4 | |a Structure | |
| 650 | 4 | |a Lassa fever | |
| 650 | 4 | |a Biochemistry | |
| 650 | 4 | |a Viruses | |
| 650 | 4 | |a Biochemical analysis | |
| 650 | 4 | |a RNA viruses | |
| 650 | 4 | |a Hemorrhage | |
| 650 | 4 | |a Public health | |
| 650 | 4 | |a Neutralizing | |
| 650 | 4 | |a Fever | |
| 650 | 4 | |a Antigens | |
| 650 | 4 | |a Crystal structure | |
| 650 | 4 | |a Glycoproteins | |
| 650 | 4 | |a Binding | |
| 650 | 4 | |a Neutralization | |
| 650 | 4 | |a High resolution | |
| 650 | 4 | |a Anchors | |
| 650 | 4 | |a Receptors | |
| 650 | 4 | |a Fatal | |
| 650 | 4 | |a Assembly | |
| 650 | 4 | |a Inhibition | |
| 650 | 4 | |a Monomers | |
| 650 | 4 | |a Glycoprotein | |
| 650 | 4 | |a Ribonucleic acids | |
| 650 | 4 | |a Hemorrhagic fever | |
| 650 | 4 | |a Hemorrhagic disease | |
| 650 | 4 | |a Design analysis | |
| 700 | 1 | |a Zandonatti, Michelle A |4 oth | |
| 700 | 1 | |a Kleinfelter, Lara M |4 oth | |
| 700 | 1 | |a Heinrich, Megan L |4 oth | |
| 700 | 1 | |a Rowland, Megan M |4 oth | |
| 700 | 1 | |a Chandran, Kartik |4 oth | |
| 700 | 1 | |a Branco, Luis M |4 oth | |
| 700 | 1 | |a Robinson, James E |4 oth | |
| 700 | 1 | |a Garry, Robert F |4 oth | |
| 700 | 1 | |a Saphire, Erica Ollmann |4 oth | |
| 773 | 0 | 8 | |i Enthalten in |t Science |d Washington, DC : AAAS, American Assoc. for the Advancement of Science, 1883 |g 356(2017), 6341, Seite 923 |w (DE-627)12931482X |w (DE-600)128410-1 |w (DE-576)014533189 |x 0036-8075 |7 nnns |
| 773 | 1 | 8 | |g volume:356 |g year:2017 |g number:6341 |g pages:923 |
| 856 | 4 | 1 | |u http://dx.doi.org/10.1126/science.aam7260 |3 Volltext |
| 856 | 4 | 2 | |u https://search.proquest.com/docview/1904891937 |
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| 952 | |d 356 |j 2017 |e 6341 |h 923 | ||