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BK polyomavirus infection and nephropathy: the virus–immune system interplay

Abstract

Reactivation of latent BK polyomavirus (BKV) infection continues to be a major challenge in renal graft recipients. Progression of BKV infection to BKV-associated nephropathy (BKVAN) leads to graft loss in up to 60% of affected patients. Interestingly, although >80% of healthy adults are seropositive for BKV, BKVAN occurs almost exclusively in transplanted kidneys, which raises questions about its underlying pathogenetic mechanisms. Intragraft inflammation and an insufficient antiviral immune response seem to be the most important risk factors. Early studies revealed an association between the rate of recovery of BKV-specific cellular immunity (which shows high interindividual variation) and BK viral clearance, which determines the clinical course of BKV infection. In patients with prompt recovery of BKV-specific T cells, BKV infection can be controlled at the early reactivation stage and does not progress to BKVAN. By contrast, in patients with persistent BKV reactivation caused by insufficient BKV-specific immunity, continued viral replication and inflammation ultimately lead to graft injury and/or BKVAN. As the chronic course of BKV infection can be prevented in most patients by prompt restoration of BKV-specific immunity, frequent monitoring of BK viral load and targeted, timely modification or reduction of immunosuppression is strongly recommended for affected patients.

Key Points

  • BK polyomavirus (BKV) is a latent virus known to reactivate under immunosuppression

  • BKV-associated nephropathy (BKVAN) is a complication of active BKV infection that mainly affects renal transplant recipients

  • Intragraft inflammation and an insufficient antiviral immune response seem to be the most important risk factors for BKVAN

  • No effective, specific therapy for BKVAN currently exists

  • Frequent monitoring of BKV replication followed by judicious reduction or modification of immunosuppression (to improve antiviral immunity) is the current recommended approach for management of BKVAN

  • An immune pathogenesis might dominate in patients with persistent BKV replication; reduction of immunosuppression as a therapeutic option for BKVAN should therefore be considered with caution in such patients

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Figure 1: The functional activity of BKV-specific T cells seems to determine the clinical outcome of BKV reactivation.
Figure 2: The dual role of BKV-specific cytotoxic T cells in BKV infection.

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N. Babel researched the data for and wrote the article and provided a substantial contribution to discussions of the content, review and/or editing of the manuscript before submission. H. D. Volk and P. Reinke contributed equally to discussions of the content and to review and/or editing of the manuscript before submission.

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Correspondence to Nina Babel.

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Babel, N., Volk, HD. & Reinke, P. BK polyomavirus infection and nephropathy: the virus–immune system interplay. Nat Rev Nephrol 7, 399–406 (2011). https://doi.org/10.1038/nrneph.2011.59

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