PDGFR – HCMV GB (256222)

  https://cordis.europa.eu/project/id/256222

  FP7 (2007-2013)

  Structural Studies of the Human Cytomegalovirus Glycoprotein B Activation Mechanism of PDGFR alpha

  Marie Curie Action: "Reintegration Grants" (FP7-PEOPLE-2009-RG)

  cell signaling  ·  inflammatory diseases  ·  electron microscopy  ·  oncology  ·  structural biology

  2010-04-01 Start Date (YY-MM-DD)

  2014-03-31 End Date (YY-MM-DD)

  € 100,000 Total Cost

  Description

HCMV infection is life-threatening for immuno-compromised patients, and is the most frequent cause of congenital abnormalities in Europe and the USA. HCMV infection can also lead to cardiovascular and chronic bowel inflammatory diseases and several types of cancer (the latter is still a matter of controversy). Effective treatment for HCMV disease is available, but the rapid emergence of drug resistant strains pose an urgent need to find new targets and to develop new inhibitors against HCMV. For cell invasion, and in order to carry out different parts of its life cycle, the HCMV directly manipulates normal cell signaling pathways. The HCMV envelope glycoprotein B (gB) has a versatile role in this process: first, it attaches to the host extracellular matrix - thus participating in viral absorption. Next, gB specifically binds to and activates a cell surface receptor – the Platelet Derived Growth Factor Receptor  (PDGFR) which initiates a cell-survival response, followed by a gB-mediated membrane fusion. Anti-gB neutralizing antibodies are developed, aiming to prevent HCMV infection and disease. The ultimate goal of this research is to understand the structural basis of PDGFR activation by HCMV gB. Using X-ray Crystallography and Electron Microscopy, two of the most powerful techniques in current structural biology, we specifically aim to: 1. Understand how the binding of HCMV gB results with PDGFR activation and cell signaling events. 2. Chart the gB-PDGFR interacting surfaces and define the most critical determinants in this interaction. Taken together, the expected results will shed light on a vital element in HCMV invasion and will set the ground for the design of specific inhibitors to treat HCMV infection and disease.

  Complicit Organisations

1 Israeli organisation participates in PDGFR – HCMV GB.