On April 4, 2006, PED Seminar Series Presents

Polyomavirus infection dynamics and organ pathology

by Georg Funk, PhD

Polyomavirus-associated nephropathy (PVAN) is a newly recognized cause of kidney allograft failure during the first 2 years posttransplant and affects approximately 1-10% of the patients. The human polyomavirus type 1, better known as BK virus (BKV), is the underlying etiologic agent.

Currently, no specific antivirals are available, and the mainstay of treatment is to improve immunological control by reducing immuno-suppression. These interventions are complex and often difficult to compare. Clinically, PVAN appears as a slowly progressing disorder with initially no apparent decrease in allograft function. However, high levels of BKV of 104-107 /mL are detected in the blood which decrease after intervention. Of note, surgical removal of allografts was followed by a rapid drop of BKV load in the blood suggesting that the vast majority of BKV load was derived from the transplanted kidney.

To better understand the role of the virus in the pathogenesis of PVAN, we examined for the first time the replication dynamics of BKV in renal graft recipients in vivo. We find rapid dynamics of BKV, with fast viral doubling times and half-lives in the order of 2h and a viral generation time of about 2 days. These data are in contrast to widely held beliefs in the field, which still characterizes BKV as a ‘slowly’ replicating virus. Moreover, our results emphasize host cell lysis as a major pathogenetic factor in PVAN.

Based on the replication parameters, we explore R0 as a simple measure for quantifying and comparing complex therapeutic interventions required for BKV in clinical studies.

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