on June 6, 2016
A publication in the scientific journal Nature Microbiology identifies PDGFRα as the receptor for the trimeric gHgLgO complex of Human cytomegalovirus (HCMV). The study led by the Institute for Research in Biomedicine (IRB) affiliated to the Università della Svizzera italiana (USI) was done in collaboration with scientists from Humabs BioMed SA in Switzerland, the IRCCS Policlinico San Matteo, the Istituto Nazionale Genetica Molecolare in Milan, in Italy and the Vaccine Research Center (VRC) of the American National Institutes of Health (NIH).
Background
HCMV is a widespread pathogen with a very high sero-prevalence in humans worldwide. HCMV infection in utero is the leading viral cause of congenital birth defects. In healthy individuals HCMV establishes lifelong latency, but in immunocompromised patients, viral reactivation can lead to severe clinical symptoms, such as disseminated viral infection, blindness and potentially cancer.
The discovery
The new study identified the Platelet-derived growth factor receptor alpha (PDGFRα), as a key molecule for viral entry of HCMV. PDGFRα is a cell surface tyrosine kinase receptor involved in organ development and tumor progression, it is present in multiple cell types such as mesenchymal cells, neurons, astrocytes, megakaryocytes and oligodendrocyte progenitor.
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| Illustration of HCMV entry mechanism by PDGFRα into fibroblastic cells. Art design Anna von Heyl. |
The study also reports the structural details of the viral gHgLgO complex bound to the cellular PDGFRα, demonstrating that the gO molecule is essential for the binding to PDGFRα and thus represents the key component that triggers the infection of the host. The discovery of the cellular receptor for HCMV represents a new step toward the control of this highly prevalent human pathogen.
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| Model of HCMV trimer (gray) interacting with PDGFR (gold). |
About the Institute for Research in Biomedicine (IRB) and the Università della Svizzera italiana (USI). The Institute for Research in Biomedicine (IRB), founded in 2000 in Bellinzona, has been affiliated to the Università della Svizzera italiana (USI) in 2010. Financed by private and public institutions, and by competitive grants, the IRB currently hosts ten research groups and 100 researchers. Research focuses on the human host defense against infections, tumors and degenerative diseases. With more than 480 publications in leading scientific journals, the IRB has gained an international reputation as a center of excellence in immunology. www.irb.usi.ch
Article
Platelet-derived growth factor-α receptor is the cellular receptor for human cytomegalovirus gHgLgO trimer.
Anna Kabanova, Jessica Marcandalli, Tongqing Zhou, Siro Bianchi, Ulrich Baxa, Yaroslav Tsybovsky, Daniele Lilleri, Chiara Silacci-Fregni, Mathilde Foglierini, Blanca Maria Fernandez-Rodriguez, Aliaksandr Druz, Baoshan Zhang, Roger Geiger, Massimiliano Pagani, Federica Sallusto, Peter D. Kwong, Davide Corti, Antonio Lanzavecchia & Laurent Perez
Nature Microbiology Article number: 16082 (2016)
DOI: 10.1038/nmicrobiol.2016.82
http://www.nature.com/articles/nmicrobiol201682
