Dataset Information

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.

SUBMITTER: Wallach T

PROVIDER: S-EPMC9880480 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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Publications

Distinct SARS-CoV-2 RNA fragments activate Toll-like receptors 7 and 8 and induce cytokine release from human macrophages and microglia.

Wallach Thomas T Raden Martin M Hinkelmann Lukas L Brehm Mariam M Rabsch Dominik D Weidling Hannah H Krüger Christina C Kettenmann Helmut H Backofen Rolf R Lehnardt Seija S

Frontiers in immunology 20230113

<h4>Introduction</h4>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.<h4>Methods</h4>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 rec ...[more]

PMID: 36713399

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Dataset Information

Distinct SARS-CoV-2 RNA fragments activate Toll-like receptors 7 and 8 and induce cytokine release from human macrophages and microglia.

Introduction

Methods

Results

Discussion

Publications

Distinct SARS-CoV-2 RNA fragments activate Toll-like receptors 7 and 8 and induce cytokine release from human macrophages and microglia.

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