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ORIGINAL RESEARCH article

Front. Immunol.
Sec. Viral Immunology
Volume 15 - 2024 | doi: 10.3389/fimmu.2024.1447980

Torque Teno Viruses Exhaust and Imprint the Human Immune System via the HLA-E/NKG2A Axis

Provisionally accepted

The final, formatted version of the article will be published soon.

    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 TTVspecific 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 TTVencoded 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.

    Keywords: TTV, Torque teno virus, NKG2A, HLA-E, Immune Evasion, Immune Regulation

    Received: 12 Jun 2024; Accepted: 09 Aug 2024.

    Copyright: © 2024 Vietzen, Simonitsch, Friedel, Berger, Kühner, Furlano, Florian, Goerzer, Koblischke, Aberle and Puchhammer-Stöckl. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Hannes Vietzen, Medical University of Vienna, Vienna, Austria

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