Role of Human Cytomegalovirus in the Acceleration of Vascular Disease
EMSL Project ID
31691
Abstract
While the identification and functional characterization of HLA alleles have had widespread success in reducing the incidence of organ rejection immediately following transplantation, infection with human cytomegalovirus (HCMV) continues to pose a significant challenge in preventing chronic rejection. The rate of cardiac graft failure within 5 years nearly doubles in the presence of HCMV infection, and similar prognoses are observed for other solid organ transplants. HCMV is easily transmitted through person-to-person contact, such as kissing, sexual contact, or even as simple as getting someone elseâ??s saliva or other bodily fluid on your hand and then touching your mouth or nose. Primary HCMV infection results in life long persistence of the virus in a latent state and reactivation of latent virus is considered to be a major source of virus in immunocompromised individuals, such as organ transplant recipients. The CDC estimates 50 â?? 80% of adults in the US are infected with HCMV by the age of 40, and there is currently no FDA-approved vaccine. HCMV infection can lead to acceleration of vascular diseases, such as atherosclerosis, restenosis, and transplant vascular sclerosis (TVS), which is a major cause of chronic organ rejection. Genomic and proteomic studies conducted in collaboration between Jay Nelsonâ??s lab (Oregon Health Sciences University) and Richard Smithâ??s lab (PNNL) have identified several factors involved in wound healing (WH) and angiogenesis (AG) induced exclusively in the presence of HCMV infection that contribute to vascular disease. This NIH funded study has 2 primary goals: 1. to determine the spectrum of cytokines and growth factors in the HCMV secretome that induce AG and WH, and 2. to correlate individual genes within the HCMV genome with the observed pro-inflammatory response, as these viral factors represent potential therapeutic targets. To achieve these goals, we, as EMSL resource owners, propose to identify tryptic peptides derived from HCMV- and mock-treated supernatant samples. Peptides will be split into 25 SCX fractions, separated by capillary RP-HPLC, and identified by a ThermoFinnigan-LTQ ion trap mass spectrometer, ~84 h of instrument run time using a 100 min elution gradient will complete the study.
Project Details
Start Date
2009-02-02
End Date
2012-02-05
Status
Closed
Released Data Link
Team
Principal Investigator
Team Members