Longitudinal alterations in the Urinary Virome of Kidney Transplant Recipients are Influenced by BK viremia and Patient Sex

Abstract Little is known about the urinary virome and how it interacts with the host, particularly in renal transplant diseases. Using metagenomic sequencing, we characterized the urinary virome of 23 kidney transplant recipients longitudinally (11 BKV + patients and 12 BKV- patients). We applied linear mixed effects models, PERMANOVA, k-means clustering and MaAsLin2 algorithms to determine virome signatures associated with post-transplant time, BK viremia status, and patient sex. We found that the richness and alpha diversity of urinary virome was significantly different in renal transplant recipients with BKV + over time in comparison to BKV- (richness p = 0.012, alpha p < 0.0001). Female BKV- patients had significantly higher virome richness than males (p = 0.0063). Virome beta diversity was significantly different between patients by BKV status (p < 0.001). Additionally, we identified underlying interactions between patient sex and BKV status, in terms of virome beta diversity (p = 0.008). BK polyomavirus infections were primarily of subtypes IA, IB1 and IB2. The non-BK dominant samples clustered into 6 urinary virome community states. BKV- samples had more anelloviruses than BKV + samples, though this difference was not statistically significant. Lastly, we identified specific viruses, associated with BKV + and time in our samples. Our results indicate that dynamic alterations in the urinary virome over the post-transplant period in kidney transplant recipients can be shaped by BK viremia and patient sex. These findings advance our fundamental understanding of the urinary virome and supports a new line of investigation in renal disease and transplantation.