Acceleration of allograft failure by cytomegalovirus

Abstract

A number of human herpesviruses are important opportunistic pathogens that have been associated with increased morbidity and mortality in transplant recipients including human cytomegalovirus (HCMV), HHV6, HHV7, HHV8 as well as HSV-1, VZV. However, HCMV has been linked both epidemiologically and through the use of animal models to the acceleration of acute and chronic allograft rejection. This review will cover the pathophysiology, epidemiology, and mechanisms of CMV-associated disease in the setting of transplantation.

Figure 1. Role of Cytomegalovirus Accelerated Chronic Allograft Rejection

In chronically infected human SOT recipients, CMV reactivates from latently infected monocytes or endothelial cells (EC) in the presence of the inflammatory alloreactive environment of the allograft. EC injury is an important first step in the development of vascular disease associated with CR. The response to injury involves the local release of growth factors, chemokines, and cytokines, as well as the up-regulation of adhesion molecules on the EC, which together promote monocyte/macrophage migration and platelet adherence to the injured site. Wound repair and angiogenesis processes drive SMC migration and proliferation in the affected blood vessels, which leads to eventual vessel narrowing, occlusion, and graft failure due to ischemia.