Journal
SCIENCE
Volume 371, Issue 6528, Pages 482-+Publisher
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.abd0811
Keywords
-
Categories
Funding
- European Research Council [ERC-2014-CoG-647858 GENESIS, ERC-2018-CoG-817798 ProDAP]
- Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) [DFG TRR 237/A07, 1335/P015, 360372040, SPP 1923, 273898015, TRR 179/TP11, 272983813]
- ERC [ERC-2018-StG-804098 REPLISOMEBYPASS]
- Max Planck Society
Ask authors/readers for more resources
Inflammasomes play a crucial role as intracellular sensors in pathogen infection and cellular perturbation. Human NLRP1 has been identified as a direct sensor for dsRNA, triggering activation during RNA virus infection. The NLRP1 complex binds dsRNA through its leucine-rich repeat domain, leading to activation through adenosine triphosphatase activity in its NACHT domain.
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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available