Human cytomegalovirus (HCMV) has been proposed to be a risk factor for transplant-associated atherosclerosis, restenosis, and atherosclerosis in some individuals with no known risk factors. This hypothesis has received increasing support as a result of epidemiological data, clinical observations, animal research, and in vitro studies with smooth muscle cells, endothelial cells, and monocyte/macrophages. The long term goals of this study are to determine how HCMV mediates this process. This study will focus on how IE2 86, an essential viral protein, affects signaling pathways in human aortic endothelial cells.
The first aim of this study is to examine how two specific IE2 86 mutants will affect signaling pathways in human aortic endothelial cells. The three major pathways of interest include the endothelial nitric oxide synthase pathway, the regulation of the endothelial cell protein C receptor, and the regulation of p53 localization and activity. These pathways will be examined by generating recombinant viruses as BACs in the TR clinical isolate of HCMV and examining the effects in human aortic endothelial cells.
The second aim i s to examine which viral and cellular proteins interact with IE2 86. This will be achieved by introducing a tandem affinity purification tag into the endogenous IE2 86 protein. These interactions will be further elucidated by examining the two specific IE2 86 mutants studied in Aim 1. It is believed that human cytomegalovirus (HCMV) plays a role in vascular diseases such as atherosclerosis. Because the virus affects between 60-90% of the U.S. population it is important to determine how HCMV causes vascular disease.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Individual Predoctoral NRSA for M.D./Ph.D. Fellowships (ADAMHA) (F30)
Project #
5F30HL094041-03
Application #
7903216
Study Section
Special Emphasis Panel (ZRG1-F10-H (21))
Program Officer
Meadows, Tawanna
Project Start
2008-08-05
Project End
2013-08-04
Budget Start
2010-08-05
Budget End
2011-08-04
Support Year
3
Fiscal Year
2010
Total Cost
$31,414
Indirect Cost
Name
University of California San Diego
Department
Other Basic Sciences
Type
Schools of Medicine
DUNS #
804355790
City
La Jolla
State
CA
Country
United States
Zip Code
92093