ArticleTranslational andrology and urology2025
Digital spatial profiling reveals the molecular signatures of BK virus infection in renal transplant recipients.
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Abstract
Background: BK polyomavirus-associated nephropathy (BKVAN) is a major cause of graft dysfunction in kidney transplant recipients, and is often triggered by BK virus reactivation due to immunosuppression. This study used GeoMx digital spatial profiling (DSP) to investigate molecular changes during BK virus infection. Methods: Eight formalin-fixed and paraffin-embedded (FFPE) kidney samples from the following three groups were analyzed: the normal function (n=3), BK polyomavirus viremia (BKV) (n=2), and BKVAN (n=3) groups. Transcriptional changes in epithelial cells, immune cells, and fibroblasts were assessed. Immune microenvironment alterations were analyzed through cellular deconvolution. Results: Distinct molecular signatures were observed across the infection stages and cell types, of which, epithelial cells showed significant dysregulation and unique involvement in ribosomal protein synthesis. The pathway analysis revealed that the pathways associated with viral infection, allogeneic rejection, and immunity (antigen presentation, chemokines, and inflammation) were significantly enriched during BKVAN progression. The key genes associated with BK polyomavirus (BKPyV) infection ( Conclusions: DSP highlighted inter- and intra-patient heterogeneity, offering insights into the molecular mechanisms underlying BKVAN and potential targets for therapeutic intervention.
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