2. Academic Validation
  3. An Unbiased Screen for Human Cytomegalovirus Identifies Neuropilin-2 as a Central Viral Receptor

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

  • Cell. 2018 Aug 23;174(5):1158-1171.e19. doi: 10.1016/j.cell.2018.06.028.
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
Affiliations

Affiliations

  • 1 Microchemistry, Proteomics and Lipidomics, Genentech, South San Francisco, CA, USA. Electronic address: martinez-martin.nadia@gene.com.
  • 2 Università della Svizzera italiana (USI), Faculty of Biomedical Sciences, Institute for Research in Biomedicine, Bellinzona, Switzerland.
  • 3 Structural Biology, Genentech, South San Francisco, CA, USA.
  • 4 Università della Svizzera italiana (USI), Faculty of Biomedical Sciences, Institute for Research in Biomedicine, Bellinzona, Switzerland; Institute of Microbiology, ETH Zürich, Zürich, Switzerland.
  • 5 Università della Svizzera italiana (USI), Faculty of Biomedical Sciences, Institute for Research in Biomedicine, Bellinzona, Switzerland; Swiss Institute of Bioinformatics (SIB), Lausanne, Switzerland.
  • 6 Bio-Molecular Resources, Genentech, South San Francisco, CA, USA.
  • 7 Department of Biology, Institute of Molecular Systems Biology, ETH Zürich, 8093 Zürich, Switzerland.
  • 8 Università della Svizzera italiana (USI), Faculty of Biomedical Sciences, Institute for Research in Biomedicine, Bellinzona, Switzerland. Electronic address: laurent.perez@irb.usi.ch.
  • 9 Structural Biology, Genentech, South San Francisco, CA, USA. Electronic address: ciferri.claudio@gene.com.
PMID: 30057110 DOI: 10.1016/j.cell.2018.06.028
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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