Distinct SARS-CoV-2 RNA fragments activate Toll-like receptors 7 and 8 and induce cytokine release from human macrophages and microglia
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
- Location
-
Deutsche Nationalbibliothek Frankfurt am Main
- Extent
-
Online-Ressource
- Language
-
Englisch
- Notes
-
Frontiers in immunology. - 13 (2023) , 1066456, ISSN: 1664-3224
- Event
-
Veröffentlichung
- (where)
-
Freiburg
- (who)
-
Universität
- (when)
-
2023
- Creator
-
Wallach, Thomas
Raden, Martin
Hinkelmann, Lukas
Brehm, Mariam
Rabsch, Dominik
Weidling, Hannah
Krüger, Christina
Kettenmann, Helmut
Backofen, Rolf
Lehnardt, Seija
- DOI
-
10.3389/fimmu.2022.1066456
- URN
-
urn:nbn:de:bsz:25-freidok-2341501
- Rights
-
Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
- Last update
-
14.08.2025, 10:58 AM CEST
Data provider
Deutsche Nationalbibliothek. If you have any questions about the object, please contact the data provider.
Associated
- Wallach, Thomas
- Raden, Martin
- Hinkelmann, Lukas
- Brehm, Mariam
- Rabsch, Dominik
- Weidling, Hannah
- Krüger, Christina
- Kettenmann, Helmut
- Backofen, Rolf
- Lehnardt, Seija
- Universität
Time of origin
- 2023
Other Objects (12)
Expressivity and decidability of first-order languages over feature trees
Expressivity and decidability of first-order languages over feature trees
A complete axiomatization of a theory with feature and arity constraints
Regular path expressions in feature logic
A complete and recursive feature theory
A complete and recursive feature theory
StoatyDive: evaluation and classification of peak profiles for sequencing data
A complete axiomatization of a theory with feature and arity constraints
Ant colony optimization based inverse folding of mono- and bistable RNA macromolecules
Using local RNA secondary structures for computational comparison and clustering of RNA molecules
Linking typed feature formalisms and terminological knowledge representation languages in natural language front ends
Computational analysis and prediction of RNA-RNA interactions : = Computergestützte Analyse und Vorhersage von RNA-RNA-Interaktionen
Expressivity and decidability of first-order languages over feature trees
Expressivity and decidability of first-order languages over feature trees
A complete axiomatization of a theory with feature and arity constraints
Regular path expressions in feature logic
A complete and recursive feature theory
A complete and recursive feature theory
StoatyDive: evaluation and classification of peak profiles for sequencing data
A complete axiomatization of a theory with feature and arity constraints
Ant colony optimization based inverse folding of mono- and bistable RNA macromolecules
Using local RNA secondary structures for computational comparison and clustering of RNA molecules
Linking typed feature formalisms and terminological knowledge representation languages in natural language front ends
Computational analysis and prediction of RNA-RNA interactions : = Computergestützte Analyse und Vorhersage von RNA-RNA-Interaktionen
Expressivity and decidability of first-order languages over feature trees
Expressivity and decidability of first-order languages over feature trees
A complete axiomatization of a theory with feature and arity constraints
Regular path expressions in feature logic
A complete and recursive feature theory
A complete and recursive feature theory
StoatyDive: evaluation and classification of peak profiles for sequencing data
A complete axiomatization of a theory with feature and arity constraints
Ant colony optimization based inverse folding of mono- and bistable RNA macromolecules
Using local RNA secondary structures for computational comparison and clustering of RNA molecules
Linking typed feature formalisms and terminological knowledge representation languages in natural language front ends