IGF1R is an entry receptor for respiratory syncytial virus

Cameron D. Griffiths, Leanne M. Bilawchuk, John E. McDonough, Kyla C. Jamieson, Farah Elawar, Yuchen Cen, Wenming Duan, Cindy Lin, Haeun Song, Jean-Laurent Casanova, Steven Ogg, Lionel Dylan Jensen, Bernard Thienpont, Anil Kumar, Tom C. Hobman, David Proud, Theo J. Moraes and David J. Marchant ()
Additional contact information
Cameron D. Griffiths: University of Alberta
Leanne M. Bilawchuk: University of Alberta
John E. McDonough: Yale University School of Medicine
Kyla C. Jamieson: University of Calgary
Farah Elawar: University of Alberta
Yuchen Cen: Hospital for Sick Children Research Institute
Wenming Duan: Hospital for Sick Children Research Institute
Cindy Lin: Hospital for Sick Children Research Institute
Haeun Song: Hospital for Sick Children Research Institute
Jean-Laurent Casanova: The Rockefeller University
Steven Ogg: University of Alberta
Lionel Dylan Jensen: University of Alberta
Bernard Thienpont: KU Leuven
Anil Kumar: University of Alberta
Tom C. Hobman: University of Alberta
David Proud: University of Calgary
Theo J. Moraes: Hospital for Sick Children Research Institute
David J. Marchant: University of Alberta

Nature, 2020, vol. 583, issue 7817, 615-619

Abstract: Abstract Pneumonia resulting from infection is one of the leading causes of death worldwide. Pulmonary infection by the respiratory syncytial virus (RSV) is a large burden on human health, for which there are few therapeutic options1. RSV targets ciliated epithelial cells in the airways, but how viruses such as RSV interact with receptors on these cells is not understood. Nucleolin is an entry coreceptor for RSV2 and also mediates the cellular entry of influenza, the parainfluenza virus, some enteroviruses and the bacterium that causes tularaemia3,4. Here we show a mechanism of RSV entry into cells in which outside-in signalling, involving binding of the prefusion RSV-F glycoprotein with the insulin-like growth factor-1 receptor, triggers the activation of protein kinase C zeta (PKCζ). This cellular signalling cascade recruits nucleolin from the nuclei of cells to the plasma membrane, where it also binds to RSV-F on virions. We find that inhibiting PKCζ activation prevents the trafficking of nucleolin to RSV particles on airway organoid cultures, and reduces viral replication and pathology in RSV-infected mice. These findings reveal a mechanism of virus entry in which receptor engagement and signal transduction bring the coreceptor to viral particles at the cell surface, and could form the basis of new therapeutics to treat RSV infection.

Date: 2020
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41586-020-2369-7 Abstract (text/html)
Access to the full text of the articles in this series is restricted.

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:nature:v:583:y:2020:i:7817:d:10.1038_s41586-020-2369-7

Ordering information: This journal article can be ordered from
https://www.nature.com/

DOI: 10.1038/s41586-020-2369-7

Access Statistics for this article

Nature is currently edited by Magdalena Skipper

More articles in Nature from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().