Metagenomic Virome Sequencing in Living Donor and Recipient Kidney Transplant Pairs Revealed JC Polyomavirus Transmission

Abstract

Background. Before kidney transplantation, donors and recipients are routinely screened for viral pathogens using specific tests. Little is known about unrecognized viruses of the urinary tract that potentially result in transmission. Using an open metagenomic approach, we aimed to comprehensively assess virus transmission in living-donor kidney transplantation.Methods. Living kidney donors and their corresponding recipients 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 and urine samples were collected and transplant recipients were evaluated for signs of infection or other transplant-related complications. For metagenomic analysis, samples were enriched for viruses, amplified by anchored random polymerase chain reaction (PCR), and sequenced using high-throughput metagenomic sequencing. Viruses detected by sequencing were confirmed using real-time PCR.Results. We analyzed a total of 30 living kidney donor and recipient pairs, with a follow-up of at least 1 year. In addition to viruses commonly detected during routine post-transplant virus monitoring, metagenomic sequencing detected JC polyomavirus (JCPyV) in the urine of 7 donors and their corresponding recipients. Phylogenetic analysis confirmed infection with the donor strain in 6 cases, suggesting transmission from the transplant donor to the recipient, despite recipient seropositivity for JCPyV at the time of transplantation.Conclusions. Metagenomic sequencing identified frequent transmission of JCPyV from kidney transplant donors to recipients. Considering the high incidence rate, future studies within larger cohorts are needed to define the relevance of JCPyV infection and the donor's virome for transplant outcomes.

JC polyomavirus‐specific antibody responses in pediatric kidney transplant recipients

“…However, the widespread JCPyV infection in the general adult population and the frequent shedding of JCPyV in the urine suggest that this is likely to be a relevant source especially among the seroconverters in the first 6 months post‐transplant. Indeed, deep‐sequencing data from adult KTR support the donor‐derived transmission in a substantial number of patients, independently of the positive serostatus at transplant . From our serological study, one can cautiously hypothesize that JCPyV replication and exposure occurs during the first 2 years post‐transplant with the functional impact seen at 48 months.…”

“…JCPyV-specific antibodies were tested using the Vp1-VLP-based ELISA described previously. 15,20 JCPyV-IgG levels were measured in a standardized fashion together with an internal reference serum to obtain a nOD. Briefly, 384-well microplates (Greiner, Cat.-no.…”

“…Accordingly, little is known about primary JCPyV infection and seroconversion in KTR, and most information on JCPyV replication and disease is obtained from adult KTR. Recently, transmission of donor‐derived JCPyV was identified by next‐generation sequencing in seropositive adult KTR . However, given the lower JCPyV seroprevalence of <50% in children under 10 years of age, primary JCPyV infection after KT either through the transplant or following natural exposure post‐transplant are plausible scenarios in pediatric KTRs.…”

Urobiome: In Sickness and in Health

“…Another study of Schreiber et al used metagenomic virome sequencing and found JCV in the urine of kidney donors and recipients at the time of transplantation as well as in recipients 4–6 weeks and/or 1 year post transplant. However, despite JCV positivity at the time of transplantation, phylogenetic analysis revealed the domination of donor-derived JCV strains [41]. The study of Santiago-Rodriguez et al [34] on patients with urinary tract infection (UTI) did not establish a significant difference between the virome from UTI patients and those without UTIs.…”

Blood Virosphere in Febrile Tanzanian Children

“…The human virome has been described in stool, skin, nasopharyngeal swabs or breast milk [4]. Investigations were also undertaken on blood from individuals representing the general population [5], blood donors [6][7][8][9], and in subjects with various conditions such as transplant recipients [10][11][12], individuals living with HIV [13], and febrile adult and paediatric patients [1,[14][15][16][17][18]. However, most of these studies were limited by the scope of their analyses (e.g.…”