Human Polyomavirus (HPyV) and Organ Transplantation

Abstract

Human polyomaviruses are ubiquitous in the general population. In immune competent individuals, primary infection is usually asymptomatic, with lifelong viral persistence without serious clinical manifestations. Host immunological perturbations are associated with reactivation of these latent viruses and can result in a wide range of clinical presentations. For example, reemergence of this disease during the past two decades has been attributed to the use of potent maintenance immunosuppression (IS) therapy. Though recipients of kidney transplants are at increased risk of developing PyV reactivation compared to other solid organ transplants despite the use of similar types of IS therapy, this paradox remains poorly understood. The most common polyomaviral disease in recipients of kidney transplants is reactivation of BKPyV, leading to asymptomatic viruria in 30–50 % and viremia (20–25 %). Progression in viremia results in end organ damage, such as ureteral ulceration and ureteral stenosis; allograft nephropathy with special histological characteristics (PyVaN) develops in nearly 5–10 % of recipients, and graft failure develops in 45–70 % of patients with PyVAN. Nonrenal manifestations include skin lesions including skin rash (trichodysplasia spinulosa-associated skin disease due to TSPyV) and skin cancers (Merkel cell carcinoma), progressive multifocal leukoencephalopathy (PML) and rarely fatal vasculopathic illness, bladder cancer, and hemophagocytic syndrome. Increased net immunosuppression may be one of the factors that impair the immune effector mechanisms that allow polyomaviral replication. Thus interventions that can restore polyoma-specific immunity can abrogate viral replication. Based on this contemporary notion, reduction in maintenance IS therapy is an effective first-line therapy that has been shown to ameliorate viral load but may not be enough to result in sustained viral response. However, early detection of viremia with prospective monitoring by quantitative polymerase chain reaction has been defined as preemptive diagnosis. It is recommended that viremia should be monitored at frequent intervals during the first year of transplant. If viremia is persistent on more than two occasions, it should be treated with careful and prudent reduction in the intensity of baseline IS therapy. Currently there are no antipolyomaviral agents of proven efficacy and safety. Polyomaviral-directed active immunotherapy holds promise in the management of different clinical syndromes associated with polyomaviral reactivation in immunocompromised host.