The impact of cytomegalovirus in renal transplant recipients
An important strategy to prevent rejection after renal transplantation is suppression of the immune system of the recipient by medication. However, the diminished immune response also impairs the protection against viral infections, of which human cytomegalovirus (CMV) is the most prominent after renal transplantation. We describe the impact of CMV on renal transplant recipients, with underlying mechanisms and potential targets for therapeutic intervention. Data concerning clinical and experimental virology, transplantation and kidney function are combined to further understand the role of CMV on the patient, kidney and cell. We demonstrate the lasting loss of renal function in patients with pronounced CMV infection (both in extent and duration) after transplantation, and for those with a delayed antibody response to CMV. Next to the effect of immune suppressive medication, immune cells with regulatory potential might down-modulate the immune response. CMV infection was more prominent in patients with high number of regulatory immune cells. The CMV virus also utilizes immunomodulating strategies to evade the antiviral response, for example by expressing viral chemokine receptor US28. We have demonstrated US28 in the vascular wall of kidneys after transplantation, and show that the presence of US28 significantly accelerates viral spreading, predominantly through cell-to-cell contact. It does not only contribute to lytic cell death, but also to abnormal cell metabolism, which might contribute to the vasculopathy seen in transplanted kidneys. Our findings provide important insights into the effects of CMV infection with potential targets for therapeutic intervention, and contribute to improving the long-term success of renal transplantation.