ROLE OF THE CYTOMEGALOVIRUS SECRETOME IN ACCELERATION OF TVS

Oregon Health & Science University, Portland OR

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Abstract

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The long-term goal of this project is to determine the role of human cytomegalovirus (HCMV) in the acceleration of vascular diseases such as atherosclerosis, restenosis, and transplant vascular sclerosis (TVS). HCMV is associated with TVS and CR in solid organ transplant patients and we have observed that RCMV significantly accelerates the development of TVS and CR in heart allografts in the rat transplant model. Although we can detect the presence of virus in the transplanted heart throughout the disease course, the number of infected cells in the allograft does not account for the global effects of RCMV infection of the organ in the development of TVS. This lack of correlation suggests that infected cells are influencing the microenvironment via paracrine mechanisms. Analysis of allografts with RCMV-accelerated TVS for host cell gene expression by microarray analysis revealed a significant number of genes involved in tissue remodeling (WH) and angiogenesis (AG) that were highly up-regulated in the organ transplant. We hypothesize that the spectrum of cytokines and growth factors secreted by CMV-infected cells significantly contribute to the acceleration of TVS and CR in heart allografts through the stimulation of WH and AG.