COVID-19 research

Gene: PDGFRA

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Evidence Summary from Illumina curation team: The PDGFRA gene encodes the platelet-derived growth factor receptor alpha protein, a tyrosine-protein kinase that acts as a cell-surface receptor for PDGFA, PDGFB and PDGFC, binding of which leads to the activation of several signaling cascades, and plays an essential role in the regulation of embryonic development, cell proliferation, survival and chemotaxis. PDGFRA has been demonstrated to be a critical receptor for human cytomegalovirus infection (PMID 18701889: Soroceanu et al. 2008). Di Pasquale et al. (2003) (PMID 14502277). also confirmed the role of PDGFRA and PDGFRB as receptors for adeno-associated virus type 5 (AAV-5). PMID 18701889: Soroceanu et al. 2008 - PDGFRA is specifically phosphorylated by both laboratory and clinical isolates of human cytomegalovirus (CMV) in various human cell types, resulting in activation of the phosphoinositide-3-kinase signaling pathway. Cells in which PDGFRA was genetically deleted or functionally blocked were nonpermissive to human CMV entry, viral gene expression, or infectious virus production. Reintroducing the human PDGFRA gene into knockout cells restored susceptibility to viral entry and essential viral gene expression. Blockade of receptor function with a humanized PDGFRA blocking antibody (IMC-3G3) or targeted inhibition of its kinase activity with a small molecule (Gleevec) completely inhibited human CMV viral internalization and gene expression in human epithelial, endothelial, and fibroblast cells. Viral entry in cells harboring endogenous PDGFRA was competitively inhibited by pretreatment with PDGF-AA. It was demonstrated that human CMV glycoprotein B directly interacts with PDGFRA, resulting in receptor tyrosine phosphorylation, and that glycoprotein B neutralizing antibodies inhibit human CMV-induced PDGFRA phosphorylation. The authors concluded that PDGFRA is a critical receptor required for human CMV infection, and thus a target for novel antiviral therapies.

Created: 28 May 2020, 3:12 p.m. | Last Modified: 28 May 2020, 3:12 p.m.

Panel Version: 0.347

Publications

• 18701889
• 14502277

Identified through an OMIM search for potential viral susceptibility genes, and subsequently triaged/reviewed by Illumina curation team.

Created: 28 May 2020, 12:36 p.m. | Last Modified: 28 May 2020, 12:36 p.m.

Panel Version: 0.336