Tumor necrosis factor-alpha blockade suppresses BK polyomavirus replication

Yi Jung Li, Jiun Wen Wang, Hsin Hsu Wu, Hsu Han Wang, Yang Jen Chiang, Huang Yu Yang, Hsiang Hao Hsu, Chih Wei Yang, Ya Chung Tian*

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

1 Scopus citations


Purpose: BK Polyomavirus (BKPyV) infection manifests as renal inflammation and can cause kidney damage. Tumor necrosis factor-α (TNF-α) is increased in renal inflammation and injury. The aim of this study was to investigate the effect of TNF-α blockade on BKPyV infection. Methods: Urine specimens from 22 patients with BKPyV-associated nephropathy (BKPyVN) and 35 non-BKPyVN kidney transplant recipients were analyzed. Results: We demonstrated increased urinary levels of TNF-α and its receptors, TNFR1 and TNFR2, in BKPyVN patients. Treating BKPyV-infected human proximal tubular cells (HRPTECs) with TNF-α stimulated the expression of large T antigen and viral capsid protein-1 mRNA and proteins and BKPyV promoter activity. Knockdown of TNFR1 or TNFR2 expression caused a reduction in TNF-α-stimulated viral replication. NF-κB activation induced by overexpression of constitutively active IKK2 significantly increased viral replication and the activity of the BKPyV promoter containing an NF-κB binding site. The addition of a NF-κB inhibitor on BKPyV-infected cells suppressed viral replication. Blockade of TNF-α functionality by etanercept reduced BKPyV-stimulated expression of TNF-α, interleukin-1β (IL-1β), IL-6 and IL-8 and suppressed TNF-α-stimulated viral replication. In cultured HRPTECs and THP-1 cells, BKPyV infection led to increased expression of TNF-α, interleukin-1 β (IL-1β), IL-6 and TNFR1 and TNFR2 but the stimulated magnitude was far less than that induced by poly(I:C). This may suggest that BKPyV-mediated autocrine effect is not a major source of TNFα. Conclusion: TNF-α stimulates BKPyV replication and inhibition of its signal cascade or functionality attenuates its stimulatory effect. Our study provides a therapeutic anti-BKPyV target.

Original languageEnglish
Pages (from-to)967-980
Number of pages14
Issue number4
StatePublished - 08 2023

Bibliographical note

© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.


  • BK polyomavirus
  • BKPyV-associated nephropathy
  • Large T antigen
  • Nuclear factor-κB
  • Tumor necrosis factor-α
  • Polyomavirus Infections/metabolism
  • Humans
  • Receptors, Tumor Necrosis Factor, Type I
  • Inflammation
  • Tumor Necrosis Factor-alpha
  • BK Virus/genetics
  • Interleukin-6
  • NF-kappa B
  • Receptors, Tumor Necrosis Factor, Type II/genetics


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