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.
journal_name
Celljournal_title
Cellauthors
Martinez-Martin N,Marcandalli J,Huang CS,Arthur CP,Perotti M,Foglierini M,Ho H,Dosey AM,Shriver S,Payandeh J,Leitner A,Lanzavecchia A,Perez L,Ciferri Cdoi
10.1016/j.cell.2018.06.028subject
Has Abstractpub_date
2018-08-23 00:00:00pages
1158-1171.e19issue
5eissn
0092-8674issn
1097-4172pii
S0092-8674(18)30796-7journal_volume
174pub_type
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