@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},
  volume =	 {13},
  number =	 {},
  pages =	 {1066456},
  user =	 {backofen},
  pmid =	 {36713399},
  doi = 	 {10.3389/fimmu.2022.1066456},
  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.}
}