Torque teno viruses exhaust and imprint the human immune system via the HLA-E/NKG2A axis
Hannes Vietzen, Cara Simonitsch, Benjamin Friedel, S. Berger, Laura M. Kühner, Philippe L. Furlano, David M. Florian, Irene Görzer, Maximilian Koblischke, Judith H. Aberle, Elisabeth Puchhammer‐Stöckl
Abstract
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.