Discovery of cellular factors that prevent HCMV replication

  • Tortorella, Domenico D. (PI)

Project Details


Human cytomegalovirus (HCMV) is a beta herpesvirus with a seroprevalance of 60-90% amongst the population than can cause morbidity and mortality in immuno-compromised individuals. Primary infection and/or reactivation of this virus in immunocompromised individuals, such as transplant patients may result in uncontrolled virus replication and persistent virus-mediated inflammatory processes. The vascular endothelium and monocytes represent important sites of infection and dissemination in vivo during HCMV reactivation. Indeed, infected endothelial cells are assumed to contribute to hematogenous distribution of the virus, in addition to modulating inflammatory responses in infected organs and harboring virus during persistent infection. HCMV-infected endothelial cells have become a regular finding in the tissues of post-transplant patients, suggesting a significant link between HCMV infection and chronic transplant rejection, as well as transplant vascular sclerosis. Epidemiological studies have associated HCMV in the accelerated development of transplant arterial disease and atherosclerosis. It is believed that infected endothelium may initiate the vascular infiltration of inflammatory cells during bouts of HCMV reactivation, thus accelerating immune-mediated injury. HCMV is an opportunistic virus that has evolved to utilize cellular factors to proliferate within the host while avoiding immune clearance. In order for HCMV to proliferate within the host and release progeny virions, HCMV manipulates the cellular machinery by down-regulating, up-regulating or altering cellular protein function. These cellular factors are essential for HCMV to propagate in the hostile environment of the host. We hypothesize that the identification of these factors would allow for a greater understanding of how HCMV manipulates host factors to successfully proliferate in the host. In addition, these proteins as well as the cellular pathways in which they function are potential targets for therapeutic intervention. Thus, by altering the expression level of a specific protein would prevent HCMV replication. The proposal aims to discovery cellular factors that can limit HCMV proliferation using an expression cloning strategy. These proteins will provide insight into HCMV biology as well as discovery novel protein targets to limit HCMV proliferation. (AHA Program: Grant-in-Aid)

Effective start/end date1/01/1131/12/13


  • American Heart Association: $198,000.00


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