Human NLRP1 is a sensor for double-stranded RNA

Bauernfried, Stefan; Scherr, Matthias J.; Pichlmair, Andreas; Duderstadt, Karl E. and Hornung, Veit (2021): Human NLRP1 is a sensor for double-stranded RNA. In: Science, Vol. 371, No. 6528, eabd0811

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.

• Item Type: Journal article
• Faculties: Chemistry and Pharmacy
• Subjects: 500 Science > 540 Chemistry
• ISSN: 0036-8075
• Language: English