Abstract
Inflammasomes function as intracellular sensors of pathogen infection or cellular perturbation and thereby play a central role in numerous diseases. Given the high abundance of NLRP1 in epithelial barrier tissues, we screened a diverse panel of viruses for inflammasome activation in keratinocytes. We identified Semliki Forest virus (SFV), a positive-strand RNA virus, as a potent activator of human but not murine NLRP1B. SFV replication and the associated formation of double-stranded (ds) RNA was required to engage the NLRP1 inflammasome. Moreover, delivery of long dsRNA was sufficient to trigger activation. Biochemical studies revealed that NLRP1 binds dsRNA through its leucine-rich repeat domain, resulting in its NACHT domain gaining adenosine triphosphatase activity. Altogether, these results establish human NLRP1 as a direct sensor for dsRNA and thus RNA virus infection.
Dokumententyp: | Zeitschriftenartikel |
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Fakultät: | Chemie und Pharmazie |
Themengebiete: | 500 Naturwissenschaften und Mathematik > 540 Chemie |
ISSN: | 0036-8075 |
Sprache: | Englisch |
Dokumenten ID: | 96850 |
Datum der Veröffentlichung auf Open Access LMU: | 05. Jun. 2023, 15:24 |
Letzte Änderungen: | 05. Jun. 2023, 15:24 |