Polyomavirus BK replication dynamics in vivo and in silico to predict cytopathology and viral clearance in kidney transplants

G. A. Funk, R. Gosert, P. Comoli, F. Ginevri, H. H. Hirsch

Research output: Contribution to journalArticle

Abstract

Fast BK virus (BKV) replication in renal tubular epithelial cells drives polyomavirus-BK-associated nephropathy (PVAN) to premature kidney transplant (KT) failure. BKV also replicates in urothelial cells, but remains asymptomatic in two-thirds of affected KT patients. Comparing 518 day-matched plasma-urine samples from 223 KT patients, BKV loads were ∼3000-fold higher in urine than in plasma (p <0.000001). Molecular and quantitative parameters indicated that >95% of urine BKV loads resulted from urothelial replication and 7 and 6×107, respectively. BKV dynamics in both sites were only partly linked, with full and partial discordance in 36% and 32%, respectively. Viral expansion was best explained by models where BKV replication started in the kidney followed by urothelial amplification and tubular epithelial cell cross-feeding reaching a dynamic equilibrium after ∼10 weeks. Curtailing intrarenal replication by 50% was ineffective and >80% was required for clearing viremia within 7 weeks, but viruria persisted for >14 weeks. Reductions >90% cleared viremia and viruria by 3 and 10 weeks, respectively. The model was clinically validated in prospectively monitored KT patients supporting >80% curtailing for optimal interventions.

Original languageEnglish
Pages (from-to)2368-2377
Number of pages10
JournalAmerican Journal of Transplantation
Volume8
Issue number11
DOIs
Publication statusPublished - Nov 2008

Keywords

  • BK virus
  • BK virus allograft nephropathy
  • BK virus nephritis
  • Kidney
  • Kidney transplantation
  • Medical virology
  • Polyomavirus
  • Polyomavirus BK
  • Polyomavirus kinetics
  • Polyomavirus-associated nephropathy

ASJC Scopus subject areas

  • Transplantation
  • Immunology and Allergy
  • Pharmacology (medical)

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