Skip to main content
bioRxiv
  • Home
  • About
  • Submit
  • ALERTS / RSS
Advanced Search
New Results

Antibody recognition of the Pneumovirus fusion protein trimer interface

View ORCID ProfileJiachen Huang, View ORCID ProfileDarren Diaz, View ORCID ProfileJarrod J. Mousa
doi: https://doi.org/10.1101/2020.05.20.107508
Jiachen Huang
1Department of Infectious Diseases, College of Veterinary Medicine, University of Georgia, Athens, GA 30602
2Center for Vaccines and Immunology, College of Veterinary Medicine, University of Georgia, Athens, GA 30602
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Jiachen Huang
Darren Diaz
1Department of Infectious Diseases, College of Veterinary Medicine, University of Georgia, Athens, GA 30602
2Center for Vaccines and Immunology, College of Veterinary Medicine, University of Georgia, Athens, GA 30602
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Darren Diaz
Jarrod J. Mousa
1Department of Infectious Diseases, College of Veterinary Medicine, University of Georgia, Athens, GA 30602
2Center for Vaccines and Immunology, College of Veterinary Medicine, University of Georgia, Athens, GA 30602
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Jarrod J. Mousa
  • For correspondence: jarrod.mousa@uga.edu
  • Abstract
  • Full Text
  • Info/History
  • Metrics
  • Supplementary material
  • Preview PDF
Loading

Abstract

Human metapneumovirus is a leading cause of viral respiratory infection in children, and can cause severe lower respiratory infection in infants, the elderly, and immunocompromised patients. However, there remain no licensed vaccines or specific treatments for hMPV infection. Although the hMPV fusion (F) protein is the sole target of neutralizing antibodies, the immunological properties of hMPV F are still poorly understood. To further define the humoral immune response to the hMPV F protein, we isolated two new human monoclonal antibodies (mAbs), MPV458 and MPV465. Both mAbs are neutralizing in vitro and target a unique antigenic site harbored within the trimeric interface of the hMPV F protein. We determined both MPV458 and MPV465 have higher affinity for monomeric hMPV F than trimeric hMPV F. MPV458 was co-crystallized with hMPV F, and the mAb primarily interacts with an alpha helix on the F2 region of the hMPV F protein. Surprisingly, the major epitope for MPV458 lies within the trimeric interface of the hMPV F protein, suggesting significant breathing of the hMPV F protein must occur for hMPV F protein recognition of the novel epitope. In addition, significant glycan interactions were observed with a somatically mutated light chain framework residue. The data presented identifies a novel epitope on the hMPV F protein for structure-based vaccine design, and provides a new mechanism for human antibody neutralization of viral glycoproteins.

Competing Interest Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
Back to top
PreviousNext
Posted May 22, 2020.
Download PDF

Supplementary Material

Email

Thank you for your interest in spreading the word about bioRxiv.

NOTE: Your email address is requested solely to identify you as the sender of this article.

Enter multiple addresses on separate lines or separate them with commas.
Antibody recognition of the Pneumovirus fusion protein trimer interface
(Your Name) has forwarded a page to you from bioRxiv
(Your Name) thought you would like to see this page from the bioRxiv website.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Share
Antibody recognition of the Pneumovirus fusion protein trimer interface
Jiachen Huang, Darren Diaz, Jarrod J. Mousa
bioRxiv 2020.05.20.107508; doi: https://doi.org/10.1101/2020.05.20.107508
Digg logo Reddit logo Twitter logo Facebook logo Google logo LinkedIn logo Mendeley logo
Citation Tools
Antibody recognition of the Pneumovirus fusion protein trimer interface
Jiachen Huang, Darren Diaz, Jarrod J. Mousa
bioRxiv 2020.05.20.107508; doi: https://doi.org/10.1101/2020.05.20.107508

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Subject Area

  • Immunology
Subject Areas
All Articles
  • Animal Behavior and Cognition (4095)
  • Biochemistry (8786)
  • Bioengineering (6493)
  • Bioinformatics (23385)
  • Biophysics (11766)
  • Cancer Biology (9167)
  • Cell Biology (13290)
  • Clinical Trials (138)
  • Developmental Biology (7422)
  • Ecology (11386)
  • Epidemiology (2066)
  • Evolutionary Biology (15118)
  • Genetics (10413)
  • Genomics (14023)
  • Immunology (9145)
  • Microbiology (22108)
  • Molecular Biology (8793)
  • Neuroscience (47438)
  • Paleontology (350)
  • Pathology (1423)
  • Pharmacology and Toxicology (2483)
  • Physiology (3711)
  • Plant Biology (8063)
  • Scientific Communication and Education (1433)
  • Synthetic Biology (2215)
  • Systems Biology (6021)
  • Zoology (1251)