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Institute for Research in Biomedicine
Istituto di Ricerca in Biomedicina

Via Vincenzo Vela 6 - CH-6500 Bellinzona
Tel. +41 91 820 0300 - Fax +41 91 820 0302 - info [at] irb [dot] usi [dot] ch

Neuropilin-2 is a Central Viral Receptor for Human Cytomegalovirus

Research area: Immune Regulation

Researchers:

Status: In progress

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. We built a library consisting of most single transmembrane human receptors and implemented a workflow for unbiased and high-sensitivity detection of receptor-ligand interactions. We applied this technology to elucidate the long-sought receptor of human cytomegalovirus (HCMV), the leading viral cause of congenital birth defects. We identified neuropilin-2 (Nrp2) as the receptor for HCMV-pentamer infection in epithelial/endothelial cells and uncovered additional HCMV interactors. Using a combination of biochemistry, cell-based assays and electron microscopy, we characterized the pentamer-Nrp2 interaction and determined the architecture of the pentamer-Nrp2 complex.

Neuropilin-2 is a central viral receptor for Human Cytomegalovirus. Receptor validation by bio-layer interferometry, cell-based assay using CRISPR/Cas9 methodology and electron microscopy combined with cross-linking mass spectrometry