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. 2018 Aug 23;174(5):1158-1171.e19.
doi: 10.1016/j.cell.2018.06.028. Epub 2018 Jul 26.

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

Nadia Martinez-Martin  1 , Jessica Marcandalli  2 , Christine S Huang  3 , Christopher P Arthur  3 , Michela Perotti  4 , Mathilde Foglierini  5 , Hoangdung Ho  3 , Annie M Dosey  3 , Stephanie Shriver  6 , Jian Payandeh  3 , Alexander Leitner  7 , Antonio Lanzavecchia  4 , Laurent Perez  8 , Claudio Ciferri  9
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Free article

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

Nadia Martinez-Martin et al. Cell. .
Free article

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: HCMV; Neuropilin 2; Nrp2; host-pathogen interaction; human cytomegalovirus; pentamer; receptor; screen; structure; viral entry.

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