An Unbiased Screen for Human Cytomegalovirus Identifies Neuropilin-2 as a Central Viral Receptor

Details

Serval ID
serval:BIB_643513D32DF9
Type
Article: article from journal or magazin.
Collection
Publications
Title
An Unbiased Screen for Human Cytomegalovirus Identifies Neuropilin-2 as a Central Viral Receptor
Journal
Cell
Author(s)
Martinez-Martin N., Marcandalli J., Huang C. S., Arthur C. P., Perotti M., Foglierini M., Ho H., Dosey A. M., Shriver S., Payandeh J., Leitner A., Lanzavecchia A., Perez L., Ciferri C.
ISSN
0092-8674
Publication state
Published
Issued date
2018
Volume
174
Number
5
Pages
1158-1171.e19
Language
english
Notes
1097-4172
Martinez-Martin, Nadia
Marcandalli, Jessica
Huang, Christine S
Arthur, Christopher P
Perotti, Michela
Foglierini, Mathilde
Ho, Hoangdung
Dosey, Annie M
Shriver, Stephanie
Payandeh, Jian
Leitner, Alexander
Lanzavecchia, Antonio
Perez, Laurent
Ciferri, Claudio
Journal Article
Research Support, Non-U.S. Gov't
United States
Cell. 2018 Aug 23;174(5):1158-1171.e19. doi: 10.1016/j.cell.2018.06.028. Epub 2018 Jul 26.
Abstract
Characterizing cell surface receptors mediating viral infection is critical for understanding viral tropism and developing antiviral therapies. Nevertheless, due to challenges associated with detecting protein interactions on the cell surface, the host receptors of many human pathogens remain unknown. Here, we build a library consisting of most single transmembrane human receptors and implement a workflow for unbiased and high-sensitivity detection of receptor-ligand interactions. We apply this technology to elucidate the long-sought receptor of human cytomegalovirus (HCMV), the leading viral cause of congenital birth defects. We identify neuropilin-2 (Nrp2) as the receptor for HCMV-pentamer infection in epithelial/endothelial cells and uncover additional HCMV interactors. Using a combination of biochemistry, cell-based assays, and electron microscopy, we characterize the pentamer-Nrp2 interaction and determine the architecture of the pentamer-Nrp2 complex. This work represents an important approach to the study of host-pathogen interactions and provides a framework for understanding HCMV infection, neutralization, and the development of novel anti-HCMV therapies.
Keywords
Antibodies, Neutralizing/chemistry, Cell Membrane/metabolism, Cytomegalovirus/*physiology, Cytomegalovirus Infections/*metabolism, Endothelial Cells/metabolism, Epithelial Cells/metabolism, Epitope Mapping, Female, HEK293 Cells, Humans, Neuropilin-2/*metabolism, Protein Conformation, Receptors, Virus/*metabolism, Viral Envelope Proteins/metabolism, Virus Internalization, *hcmv, *Neuropilin 2, *Nrp2, *host-pathogen interaction, *human cytomegalovirus, *pentamer, *receptor, *screen, *structure, *viral entry
Create date
04/09/2020 20:03
Last modification date
07/09/2020 6:26
Usage data