Drug Discovery Opinion

DDO Limited – Consultancy for Biotech and Pharma

Aug 20 2008

Cell Receptor for HCMV Entry Identified

Posted by admin in News, tags: antiviral, HCMV, kinase

Human Cytomegalovirus (HCMV) is a member of the Herpes virus family and infects 50-80% of adults in the US. After infection, the virus remains latent in the body for the rest of the person’s life. Most people who are infected with HCMV after birth remain asymptomatic unless their immune system is compromised by drugs (transplant recipients), HIV infection or old age. In such individuals, HCMV infections can become life-threatening.

The route by which the virus enters cells is not well understood, but a report in the journal Nature now shows that the HCMV glycoprotein B binds to cell-surface platelet-derived growth factor receptor-α(PDGFR-α), which acts as an entry receptor for HCMV. PDGFR-α is a receptor tyrosine kinase, and both laboratory and clinical strains of HCMV trigger autophosphorylation of the receptor, resulting in activation of downstream signalling pathways. Cells in which PDGFR-α was genetically deleted were non-permissive to HCMV entry, viral gene expression or infectious virus production. An HCMV glycoprotein B neutralizing antibody, an antibody to PDGRF-α and Gleevec, an inhibitor of the receptor kinase activity, also completely blocked viral entry. These data suggest that PDGFR-α is critical for HCMV infection and that the receptor provides a novel target for anti-HCMV therapies.
Gleevec
PDGFRs also play an important role in angiogenesis and have been linked to the pathogenesis of some tumors. Gleevec is marketed by Novartis for treating certain types of cancer.