on July 26, 2018
A collaborative effort between the Institute for Research in Biomedicine (IRB) affiliated to the Università della Svizzera italiana (USI), Genentech, USA and the Institute of Molecular System Biology, ETH Zürich led to the identification of Neuropilin 2 as the central receptor for the pentameric complex of Human cytomegalovirus (HCMV). This study was published today in the renowned scientific journal Cell. The project was jointly conceived and supervised by Laurent Perez from the IRB and Claudio Ciferri from Genentech.
Characterization of protein mediating viral entry is necessary to understand viral tropism and develop antiviral therapies. HCMV is the most common infectious cause of permanent births defects worldwide, often resulting in newborns with auditory and cognitive abnormalities and in some cases multi-organ failure and death. So far, the receptor for the viral entry in epithelial, endothelial and myeloid cells of the HCMV had not been identified. This study describes a high-throughput screen to detect low affinity host-pathogen interactions, which led to the identification of Neuropilin 2 as a central receptor for the entry of HCMV. Neuropilin 2 is known as a cell surface glycoprotein implicated in cardiovascular and nervous system development as well as in tumorigenesis. This receptor functions help explain HCMV induced births defects listed above. In addition, the study also reports the structural details of the HCMV pentamer complex once it is bound to Neuropilin 2. The knowledge of this particular structure permits to understand and explain the very high neutralizing potency of anti-HCMV antibodies. Thus, this discovery provides very concrete insights for the development of vaccines and therapies against the highly prevalent human pathogen HCMV. This study was partly supported by the Helmut Horten Foundation, Genentech and European Research Council (Proteomics4D).
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| Potent anti-pentamer monoclonal antibodies prevent HCMV from binding to its receptor Nrp2 |
Article
An unbiased screen for Human Cytomegalovirus identifies Neuropilin-2 as a central viral receptor.
Nadia Martinez-Martin, Jessica Marcandalli, Christine S. Huang, Christopher P. Arthur, Michela Perotti, Mathilde Foglierini, Hoangdung Ho, Anne M. Dosey, Stephanie Shriver, Jian Payandeh, Alexander Leitner, Antonio Lanzavecchia, Laurent Perez*, Claudio Ciferri*
*equal contribution and correspondence.
