New study identifies PDGFRα as key molecule for HCMV viral entry

A publication in the scientific journal Nature Microbiology identifies PDGFRα as the receptor for the trimeric gHgLgO complex of Human cytomegalovirus (HCMV). TThe 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, 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.

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.