Frontiers in Immunology (Sep 2024)

Torque teno viruses exhaust and imprint the human immune system via the HLA-E/NKG2A axis

  • Hannes Vietzen,
  • Cara Simonitsch,
  • Benjamin Friedel,
  • Sarah M. Berger,
  • Laura M. Kühner,
  • Philippe L. Furlano,
  • David M. Florian,
  • Irene Görzer,
  • Maximilian Koblischke,
  • Judith H. Aberle,
  • Elisabeth Puchhammer-Stöckl

DOI
https://doi.org/10.3389/fimmu.2024.1447980
Journal volume & issue
Vol. 15

Abstract

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The ubiquitous Torque teno virus (TTV) establishes a chronically persistent infection in the human host. TTV has not been associated with any apparent disease, but, as part of the human virome, it may confer a regulatory imprint on the human immune system with as yet unclear consequences. However, so far, only few studies have characterized the TTV-specific immune responses or the overall immunological imprints by TTV. Here, we reveal that TTV infection leads to a highly exhausted TTV-specific CD8+ T-cell response, hallmarked by decreased IFN-γ production and the expression of the inhibitory NKG2A-receptor. On a functional level, we identified a panel of highly polymorphic TTV-encoded peptides that lead to an expansion of regulatory NKG2A+ natural killer, NKG2A+CD4+, and NKG2A+CD8+ T cells via the stabilization of the non-classical HLA-E molecule. Our results thus demonstrate that TTV leads to a distinct imprint on the human immune system that may further regulate overall human immune responses in infectious, autoimmune, and malignant diseases.

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