@article{Wallach_Raden_Hinkelmann-Disti_SARS_RNA-2022,
author = {Wallach, Thomas and Raden, Martin and Hinkelmann, Lukas and 
          Brehm, Mariam and Rabsch, Dominik and Weidling, Hannah and 
          Kruger, 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 = {Front Immunol},
year = {2022},
doi = {10.3389/fimmu.2022.1066456},
volume = {13},
user = {backofen},
pmid = {36713399},
pages = {1066456},
number = {},
issn = {1664-3224},
abstract = {INTRODUCTION: 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. METHODS: 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. RESULTS: 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. DISCUSSION: 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.}
}