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Peer-reviewedCC BY 4.0EMBO Molecular Medicine

A novel Torque teno virus qPCR assay reveals longitudinal viral load variability among non-immunosuppressed subjects

  • Lara Valder1
  • Thomas G Grigore1
  • Christian Schaaf2
  • Quirin Bachmann2
  • Lutz Renders2,3
  • Samuel D Jeske1,3
  • Marc Lütgehetmann4
  • Sibylle Bierbaum5
  • Hartmut Hengel5
  • Christopher Dächert6
  • Ulrike Protzer1,3,7
  • Jochen M Wettengel1,3
7 affiliations
  1. 1Technical University of Munich, School of Medicine and Health, Institute of Virology, Munich, Germany
  2. 2Technical University of Munich, School of Medicine and Health, Department of Nephrology, TUM University Hospital, Munich, Germany
  3. 3German Center for Infection Research (DZIF), Munich Partner Site, Munich, Germany
  4. 4Center for Diagnostics, Institute of Medical Microbiology, Virology and Hygiene, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
  5. 5Institute of Virology, University Medical Center, Freiburg, and Faculty of Medicine, University of Freiburg, Freiburg im Breisgau, Germany
  6. 6Ludwig Maximilian University, Max von Pettenkofer Institute and Gene Center, Virology, National Reference Center for Retroviruses, Munich, Germany
  7. 7Helmholtz Munich, Institute of Virology, Munich, Germany
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Abstract

Torque teno virus (TTV) DNA is an emerging biomarker of the individual immune status with considerable potential for guiding immunosuppressive therapy. However, widespread clinical implementation has been hampered by the lack of standardized, high-throughput diagnostic assays and limited understanding of the physiological variability of TTV viral loads over time. Here, we developed and analytically validated a novel fully automated high-throughput quantitative PCR assay for standardized TTV-DNA measurement in routine diagnostics and large-scale clinical studies. The assay demonstrated high analytical sensitivity and specificity, with a limit of detection of 32.3 copies/ml. Using this platform, we performed longitudinal profiling of plasma and serum samples collected over up to 51 months from non-immunosuppressed individuals. We observed substantial inter- and intra-individual fluctuations in TTV-DNA levels in a subset of healthy subjects, revealing intrinsic biological variability independent of immunosuppressive therapy. These findings establish a robust platform for standardized TTV monitoring while demonstrating that longitudinal viral load dynamics must be interpreted in the context of natural biological variation. Our study provides an important framework for the clinical implementation of TTV-guided immune monitoring and the need for development of evidence-based thresholds for individualized immunosuppressive therapies.

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Cite

BibTeXRIS
BibTeX
@article{valder2026novel,
  title = {{A novel Torque teno virus qPCR assay reveals longitudinal viral load variability among non-immunosuppressed subjects}},
  author = {Lara Valder and Thomas G Grigore and Christian Schaaf and Quirin Bachmann and Lutz Renders and Samuel D Jeske and Marc Lütgehetmann and Sibylle Bierbaum and Hartmut Hengel and Christopher Dächert and Ulrike Protzer and Jochen M Wettengel},
  journal = {EMBO Molecular Medicine},
  year = {2026},
  month = oct,
  doi = {10.1038/s44321-026-00540-3},
  url = {https://doi.org/10.1038/s44321-026-00540-3},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - A novel Torque teno virus qPCR assay reveals longitudinal viral load variability among non-immunosuppressed subjects
AU  - Lara Valder
AU  - Thomas G Grigore
AU  - Christian Schaaf
AU  - Quirin Bachmann
AU  - Lutz Renders
AU  - Samuel D Jeske
AU  - Marc Lütgehetmann
AU  - Sibylle Bierbaum
AU  - Hartmut Hengel
AU  - Christopher Dächert
AU  - Ulrike Protzer
AU  - Jochen M Wettengel
PY  - 2026
DA  - 2026/10/08
JO  - EMBO Molecular Medicine
DO  - 10.1038/s44321-026-00540-3
UR  - https://doi.org/10.1038/s44321-026-00540-3
AB  - Torque teno virus (TTV) DNA is an emerging biomarker of the individual immune status with considerable potential for guiding immunosuppressive therapy. However, widespread clinical implementation has been hampered by the lack of standardized, high-throughput diagnostic assays and limited understanding of the physiological variability of TTV viral loads over time. Here, we developed and analytically validated a novel fully automated high-throughput quantitative PCR assay for standardized TTV-DNA measurement in routine diagnostics and large-scale clinical studies. The assay demonstrated high analytical sensitivity and specificity, with a limit of detection of 32.3 copies/ml. Using this platform, we performed longitudinal profiling of plasma and serum samples collected over up to 51 months from non-immunosuppressed individuals. We observed substantial inter- and intra-individual fluctuations in TTV-DNA levels in a subset of healthy subjects, revealing intrinsic biological variability independent of immunosuppressive therapy. These findings establish a robust platform for standardized TTV monitoring while demonstrating that longitudinal viral load dynamics must be interpreted in the context of natural biological variation. Our study provides an important framework for the clinical implementation of TTV-guided immune monitoring and the need for development of evidence-based thresholds for individualized immunosuppressive therapies.
SN  - 1757-4676
SN  - 1757-4684
ER  -