Before kidney transplantation, donors and recipients are routinely screened for a number of active or latent viral infections using specific tests. Little is known about other, untested, apathogenic viruses a donor might carry and likely will transmit. Here, we aimed to characterize the viral metagenome of both the donor and the recipient using metagenomic sequencing at time of transplantation as well as up to one year after.
Recipients of kidney grafts and the corresponding donors were enrolled at the time of transplantation. Follow-up study visits for recipients were scheduled 4-6 weeks and 1 year thereafter. At each visit, plasma, urine and stool samples were collected and patients were evaluated for signs of infection or transplant-related complications. For metagenomic analysis, blood and urine samples were enriched for viruses, amplified using an anchored random PCR system and sequenced using high-throughput metagenomic sequencing. Viruses detected by sequencing were confirmed using real-time PCR.
We analyzed a total of 30 living kidney donor/recipient pairs with a follow up of at least 1 year. Post transplant routine virus diagnostics mainly detected cytomegalovirus (CMV) and BK polyomavirus (BKPyV) replication in blood and respiratory viruses in throat swabs. In addition to routine diagnostics, metagenomic sequencing detected JC polyomavirus (JCPyV) in urine of 7 recipients as well as all corresponding donors. Phylogenetic analysis confirmed that donor and recipient were infected with the same strain in 6 cases, suggesting a transmission from transplant donor to recipient. Moreover, Torque teno virus (TTV) was found frequently in time points after transplantation, as expected in patients under immunosuppression.
Using metagenomic sequencing, we detected transmission of JCPyV from kidney transplant donors to recipients in several cases. Future studies within larger cohorts are needed to define the relevance of the donor’s virome for the recipient, enabling the prediction of transplant outcomes.