A neutralizing antibody prevents postfusion transition of measles virus fusion protein-Reference-Cited by-同舟云学术

A neutralizing antibody prevents postfusion transition of measles virus fusion protein

Published:2024-06-28 Issue:6703 Volume:384 Page:
ISSN:0036-8075
Container-title:Science
language:en
Short-container-title:Science

Author:

Zyla Dawid S.¹^ORCID,Della Marca Roberta²³⁴^ORCID,Niemeyer Gele¹⁵^ORCID,Zipursky Gillian²³^ORCID,Stearns Kyle²³^ORCID,Leedale Cameron⁶^ORCID,Sobolik Elizabeth B.⁷^ORCID,Callaway Heather M.¹^ORCID,Hariharan Chitra¹^ORCID,Peng Weiwei⁸⁹,Parekh Diptiben¹^ORCID,Marcink Tara C.²³^ORCID,Diaz Avalos Ruben¹^ORCID,Horvat Branka¹⁰,Mathieu Cyrille¹¹^ORCID,Snijder Joost⁸⁹^ORCID,Greninger Alexander L.⁷^ORCID,Hastie Kathryn M.¹^ORCID,Niewiesk Stefan⁶^ORCID,Moscona Anne²³¹²¹³^ORCID,Porotto Matteo²³⁴^ORCID,Ollmann Saphire Erica¹¹⁴^ORCID

Affiliation:

1. Center for Vaccine Innovation, La Jolla Institute for Immunology, La Jolla, CA 92037, USA.

2. Center for Host-Pathogen Interaction, Columbia University Vagelos College of Physicians and Surgeons, New York, NY 10032, USA.

3. Department of Pediatrics, Columbia University Vagelos College of Physicians and Surgeons, New York, NY 10032, USA.

4. Department of Experimental Medicine, University of Campania “Luigi Vanvitelli,” 81100 Caserta, Italy.

5. Institute of Biochemistry, Center for Structural and Cell Biology in Medicine, University of Luebeck, D-23538 Luebeck, Germany.

6. Department of Veterinary Biosciences, College of Veterinary Medicine, The Ohio State University, Columbus, OH 43210, USA.

7. Department of Laboratory Medicine and Pathology Virology Division, University of Washington, Seattle, WA 98109, USA.

8. Biomolecular Mass Spectrometry and Proteomics, Bijvoet Center for Biomolecular Research and Utrecht Institute for Pharmaceutical Sciences, Utrecht University, 3584 CH Utrecht, Netherlands.

9. Netherlands Proteomics Center, 3584 CH Utrecht, Netherlands.

10. Immunobiology of Viral Infections, International Center for Infectiology Research-CIRI, INSERM U1111, CNRS UMR5308, University Lyon 1, ENS de Lyon, 69007 Lyon, France.

11. Centre International de Recherche en Infectiologie équipe Neuro-Invasion, TROpism and VIRal Encephalitis (NITROVIRE), INSERM U1111–Université Claude Bernard Lyon 1, CNRS, UMR5308, Ecole Normale Supérieure de Lyon, Université Lyon, 69007 Lyon, France.

12. Department of Microbiology and Immunology, Columbia University Vagelos College of Physicians and Surgeons, New York, NY 10032, USA.

13. Department of Physiology and Cellular Biophysics, Columbia University Vagelos College of Physicians and Surgeons, New York, NY 10032, USA.

14. Department of Medicine, University of California, San Diego, La Jolla, CA 92037, USA.

Abstract

Measles virus (MeV) presents a public health threat that is escalating as vaccine coverage in the general population declines and as populations of immunocompromised individuals, who cannot be vaccinated, increase. There are no approved therapeutics for MeV. Neutralizing antibodies targeting viral fusion are one potential therapeutic approach but have not yet been structurally characterized or advanced to clinical use. We present cryo–electron microscopy (cryo-EM) structures of prefusion F alone [2.1-angstrom (Å) resolution], F complexed with a fusion-inhibitory peptide (2.3-Å resolution), F complexed with the neutralizing and protective monoclonal antibody (mAb) 77 (2.6-Å resolution), and an additional structure of postfusion F (2.7-Å resolution). In vitro assays and examination of additional EM classes show that mAb 77 binds prefusion F, arrests F in an intermediate state, and prevents transition to the postfusion conformation. These structures shed light on antibody-mediated neutralization that involves arrest of fusion proteins in an intermediate state.

Publisher

American Association for the Advancement of Science (AAAS)

Link

https://www.science.org/doi/pdf/10.1126/science.adm8693

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