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BK virus infection activates the TNFα/TNF receptor system in Polyomavirus-associated nephropathy

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Abstract

Polyomavirus-associated nephropathy due to BK virus infection (BKVAN) is recognized as an important cause of significant kidney transplant dysfunction often leading to renal graft loss. The activation of innate immune defense mechanisms during BKVAN is still poorly understood and an altered regulation of inflammatory mediators by resident kidney cells upon viral infection can be expected to contribute to the onset and progression of disease. TNFα interacting with its receptors, TNF receptor 1 (TNFR1) and TNF receptor 2 (TNFR2), is largely accepted to be involved in viral responses, exhibiting both proinflammatory and immunosuppressive effects. Our aim was to examine the expressions of TNFα and TNFR1 and 2 in human collecting duct epithelial cells (HCDC) after infection with BKV as well as to study the effect of TNFα and poly(I:C), a synthetic analog of viral RNA, on the expressions of TNF receptors and proinflammatory cytokines and chemokines in HCDC. Quantitative RT-PCR analyses showed a downregulation of TNFα and an upregulation of both TNFR1 and 2 upon exposure of HCDC to the BK virus. TNFα stimulation induced the expressions of IL-6, IL-8, RANTES, and TNFR2. Poly(I:C) upregulated the expressions of both TNFR1 and TNFR2, a response that could be effectively blocked by siRNA to TLR3 and RIG-I, two double-stranded (ds) RNA receptors of the innate immune system. Poly(I:C)-dependent expression of TNFR2 but not TNFR1 was enhanced by TNFα. Taken together, our results suggest an involvement of TNF/TNFR system in virus-associated nephropathy.

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Acknowledgments

This work was supported by a grant from the Else Kröner-Fresenius-Stiftung to M.W.

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Authors and Affiliations

  1. Medizinische Klinik und Poliklinik IV, Innenstadt, Klinikum der Universität München, Ziemssenstrasse 1, 80336, Munich, Germany

    Andrea Ribeiro, Monika Merkle, Simone Köppel & Markus Wörnle

  2. Max von Pettenkofer-Institut, Munich, Germany

    Nasim Motamedi & Hans Nitschko

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  1. Andrea Ribeiro
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  2. Monika Merkle
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  3. Nasim Motamedi
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  4. Hans Nitschko
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  5. Simone Köppel
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  6. Markus Wörnle
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Correspondence to Markus Wörnle.

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Ribeiro, A., Merkle, M., Motamedi, N. et al. BK virus infection activates the TNFα/TNF receptor system in Polyomavirus-associated nephropathy. Mol Cell Biochem 411, 191–199 (2016). https://doi.org/10.1007/s11010-015-2581-1

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  • DOI: https://doi.org/10.1007/s11010-015-2581-1

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