@ARTICLE{Wallach-2023,

AUTHOR={Wallach, Thomas  and Raden, Martin  and Hinkelmann, Lukas  and Brehm, Mariam  and Rabsch, Dominik  and Weidling, Hannah  and Krüger, Christina  and Kettenmann, Helmut  and Backofen, Rolf  and Lehnardt, Seija },

TITLE={Distinct {SARS-CoV-2} {RNA} fragments activate {Toll}-like receptors 7 and 8 and induce cytokine release from human macrophages and microglia},

JOURNAL={Frontiers in Immunology},

VOLUME={13},

YEAR={2023},

DOI={10.3389/fimmu.2022.1066456},

ISSN={1664-3224},

ABSTRACT={The pandemic coronavirus disease 19 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and is marked by thromboembolic events and an inflammatory response throughout the body, including the brain.
Employing the machine learning approach BrainDead we systematically screened for SARS-CoV-2 genome-derived single-stranded (ss) RNA fragments with high potential to activate the viral RNA-sensing innate immune receptors Toll-like receptor (TLR)7 and/or TLR8. Analyzing HEK TLR7/8 reporter cells we tested such RNA fragments with respect to their potential to induce activation of human TLR7 and TLR8 and to activate human macrophages, as well as iPSC-derived human microglia, the resident immune cells in the brain.
We experimentally validated several sequence-specific RNA fragment candidates out of the SARS-CoV-2 RNA fragments predicted in silico as activators of human TLR7 and TLR8. Moreover, these SARS-CoV-2 ssRNAs induced cytokine release from human macrophages and iPSC-derived human microglia in a sequence- and species-specific fashion.
Our findings determine TLR7 and TLR8 as key sensors of SARS-CoV-2-derived ssRNAs and may deepen our understanding of the mechanisms how this virus triggers, but also modulates an inflammatory response through innate immune signaling.},
  user =         {mmann}
}