Dynamics of Human Anelloviruses in Plasma and Clinical Outcomes Following Kidney Transplantation

Abstract

Background. Torque teno virus, the major member of the genus Alphatorquevirus, is an emerging biomarker of the net state of immunosuppression after kidney transplantation. Genetic diversity constitutes a main feature of the Anelloviridae family, although its posttransplant dynamics and clinical correlates are largely unknown. Methods. The relative abundance of Alphatorquevirus, Betatorquevirus, and Gammatorquevirus genera was investigated by high-throughput sequencing in plasma specimens obtained at various points during the first posttransplant year (n = 91 recipients). Total loads of all members of the Anelloviridae family were also quantified by an “in-house” polymerase chain reaction assay targeting conserved DNA sequences (n = 195 recipients). In addition to viral kinetics, clinical study outcomes included serious infection, immunosuppression-related adverse event (opportunistic infection and cancer)‚ and acute rejection. Results. Alphatorquevirus DNA was detected in all patients at every point, with an increase from pretransplantation to month 1. A variable proportion of recipients had detectable Betatorquevirus and Gammatorquevirus at lower frequencies. At least 1 change in the predominant genus (mainly as early transition to Alphatorquevirus predominance) was shown in 35.6% of evaluable patients. Total anelloviruses DNA levels increased from baseline to month 1, to peak by month 3 and decrease thereafter, and were higher in patients treated with T-cell depleting agents. There was a significant albeit weak-to-moderate correlation between total anelloviruses and TTV DNA levels. No associations were found between the predominant Anelloviridae genus or total anelloviruses DNA levels and clinical outcomes. Conclusions. Our study provides novel insight into the evolution of the anellome after kidney transplantation.

Monitoring of plasma Torque teno virus, total Anelloviridae and Human Pegivirus 1 viral load for the prediction of infectious events and acute graft versus host disease in the allogeneic hematopoietic stem cell transplantation setting

“…To quantify TAV DNA we used an “in house” RT‐PCR that returned lower viral loads than that provided by our TTV RT‐PCR and was less sensitive, 14 despite being able to target Anelloviridae other than TTV. This extent was previously shown by our group in a cohort of SOT recipients 29 …”

“…This extent was previously shown by our group in a cohort of SOT recipients. 29 The kinetics of TTV DNA load followed a previously characterized pattern, 8,9 with lowest levels measured around the time of RNA was detected (at least in once) in around 66% of patients, a figure slightly higher than previously reported (range, 14%-61%). 17 (pretransplant) and ≥4.58 log 10 (baseline) copies/mL displayed a high sensitivity (89%) and NPV (96%) for predicting BKPyV-HC.…”

Torque Teno Virus load predicts opportunistic infections after kidney transplantation but is not associated with maintenance immunosuppression exposure.

“…Being opportunistic infection more specifically related to over-immunosuppression, it would be expected that the relationship between TTV load and opportunistic infection were stronger than with global infection, as previously reported by Doberer et al [17]. Of note, TTV load is associated with higher infection-related death even beyond the first-year post-transplantation [38].…”

Kinetics of Torque Teno Virus Viral Load Is Associated with Infection and De Novo Donor Specific Antibodies in the First Year after Kidney Transplantation: A Prospective Cohort Study

“…Abbas et al [ 25 ] demonstrated the development of a bidirectional transfer of anelloviruses between the graft and the host. As suggested by Forqué et al [ 26 ], it is plausible that the observed increase in TTV viral load between the pre- and post-transplantation periods may be partially explained by the transfer of donor’s TTV within the graft. Thus, as TTV viral load was not evaluated in donors and genotyping of TTV was not performed, we cannot differentiate between reactivation and graft-mediated infection.…”