RT Journal Article
SR Electronic
T1 SARS-CoV-2-associated ssRNAs activate inflammation and immunity via TLR7/8
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2021.04.15.439839
DO 10.1101/2021.04.15.439839
A1 Valentina Salvi
A1 Hoang Oanh Nguyen
A1 Francesca Sozio
A1 Tiziana Schioppa
A1 Mattia Laffranchi
A1 Patrizia Scapini
A1 Mauro Passari
A1 Ilaria Barbazza
A1 Laura Tiberio
A1 Nicola Tamassia
A1 Cecilia Garlanda
A1 Annalisa Del Prete
A1 Marco A. Cassatella
A1 Alberto Mantovani
A1 Silvano Sozzani
A1 Daniela Bosisio
YR 2021
UL http://biorxiv.org/content/early/2021/04/15/2021.04.15.439839.abstract
AB The inflammatory and IFN pathways of innate immunity play a key role in both resistance and pathogenesis of Coronavirus Disease 2019 (COVID-19). Innate sensors and SARS-CoV-2-Associated Molecular Patterns (SAMPs) remain to be completely defined. Here we identify single-stranded RNA (ssRNA) fragments from SARS-CoV-2 genome as direct activators of endosomal TLR7/8 and MyD88 pathway. The same sequences induced human DC activation in terms of phenotype and functions, such as IFN and cytokine production and Th1 polarization. A bioinformatic scan of the viral genome identified several hundreds of fragments potentially activating TLR7/8, suggesting that products of virus endosomal processing potently activate the IFN and inflammatory responses downstream these receptors. In vivo, SAMPs induced MyD88-dependent lung inflammation characterized by accumulation of proinflammatory and cytotoxic mediators and immune cell infiltration, as well as splenic DC phenotypical maturation. These results identify TLR7/8 as crucial cellular sensors of ssRNAs encoded by SARS-CoV-2 involved in host resistance and disease pathogenesis of COVID-19.Competing Interest StatementThe authors have declared no competing interest.