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

Transplantation. 2023 Feb 1;107(2):511-520. doi: 10.1097/TP.0000000000004292. Epub 2023 Jan 26.

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.

MeSH terms

  • Anelloviridae* / genetics
  • DNA, Viral / genetics
  • Humans
  • Immunosuppression Therapy
  • Kidney Transplantation* / adverse effects
  • Torque teno virus* / genetics
  • Viral Load

Substances

  • DNA, Viral