Endothelial and Epithelial Tropism of Human Cytomegalovirus
- Congenital Heart Disease Center
Interdisciplinary Research Initiative
2/1/2009 - 1/31/2011
Marco Colonna, J. Evan Sadler
Human cytomegalovirus (HCMV) is an important human virus particularly in pediatric settings. HCMV is a leading infectious cause of birth defects in newborns and severe disease in children receiving heart transplants. This large DNA virus encodes about 166 genes; many of them are non-essential for its infection in fibroblasts, the cell type most often used to study HCMV in culture. The central hypothesis tested in this project is that some of non-essential genes are required for HCMV infection in alternative cell types, such as epithelial cells and endothelial cells, which are natural targets for HCMV infection and central to HCMV disease in patients. A set of state-of-the-art research tools, including an infectious clone of a clinical HCMV virus TRwt and cultures of epithelial cells and endothelial cells will be used to test this hypothesis. The goals of this project are to define the infection profiles of TRwt in endothelial and epithelial cell culture models and determine the roles of previously predicted cell tropism genes in HCMV infection. This proposed study will help us to understand the mechanism of HCMV-associated vascular disease in pediatric heart transplant recipients. Ultimately the knowledge acquired from this study will be applied towards developing effective antiviral therapies to control this globally important pathogen.