Research Group

  • Dr. Susan L. Orloff, Principal Investigator
  • Dr. Daniel N. Streblow, Co-Investigator
  • Craig Kreklywich, Associate
  • Dr. Qiang Yin, Associate


  • Oregon Health Sciences University, Portland, USA


  • Role of Viral Chemokine Receptors in Cytomegalovirus-Accelerated Transplant Vascular Sclerosis

The primary cause of graft loss of all vascularized organ transplants is due to a vascular lesion associated with chronic rejection. This form of vasculopathy, referred to as transplant vascular sclerosis (TVS), is primarily characterized by concentric neointimal smooth muscle cell proliferation that results in vessel occlusion and ultimately graft failure. To date the only therapy available to treat severe TVS is re-transplantation.

Cytomegalovirus (CMV) is a ubiquitous virus that is carried in a latent form by most individuals (60–75% of the population), and is known to accelerate TVS, although through undefined mechanisms. Recently, we demonstrated that during human CMV infection of smooth muscle (SMC) the CMV-encoded chemokine receptor, US28, induces SMC migration in vitro. Rat and murine CMV also induce SMC migration of infected cells, mediated by their respective viral chemokine receptor homologues, R33 and M33. Based on our preliminary results, we hypothesize that the mechanism of CMV-accelerated TVS involves the expression of virally encoded chemokine receptors leading to intimal SMC migration, which results in the characteristic vascular lesions of TVS. Using a rat cardiac transplant model of chronic rejection we will determine the kinetics of disease progression of TVS, the extent of viral expression in tissues, the cell types and the host factors such as chemokine cytokines, and growth factors involved at various stages of the development of RCMV-induced TVS. We will then determine the effects of deletion of the CMV-encoded chemokine receptors on CMV-accelerated TVS in this cardiac transplant model. These studies will provide the molecular link to the role of CMV in the acceleration of TVS, and will serve as the basis for novel and rational design of therapeutic strategies to enhance long-term graft survival in the majority of transplant recipients, who are latently infected with CMV.