Authors
Park, S., Cho, S.-G., Chung, H. W., Hwang, S. J., Kim, T., Lee, J. M.
Abstract
Human norovirus (HNoV) is a leading cause of acute gastroenteritis, yet the mechanisms by which it interfaces with host innate immunity remain elusive. Here, we demonstrate that the HNoV NS7 protein, an RNA-dependent RNA polymerase, acts as a direct activator of canonical inflammasomes. Using reconstituted cell systems and human intestinal enteroids (HIEs), we found that NS7 interacts with both NLRP3 and NLRP6, promoting ASC speck formation, caspase-1 cleavage, and secretion of IL-1{beta} and IL-18. HNoV infection of HIEs recapitulated these events, including gasdermin D processing and robust IL-18 release. Importantly, CRISPR/Cas9-mediated NLRP6 deficiency abrogated inflammasome activation and markedly enhanced viral replication, underscoring the essential role of NLRP6 in epithelial antiviral defense. These findings identify NS7 as a novel inflammasome activator and establish NLRP6 as a key determinant of innate immune control of HNoV. Our study highlights inflammasome signaling as a potential therapeutic target for norovirus infection.
Preprint server:
bioRxiv
The authors list and abstract were imported from bioRxiv on 08 Nov 2025.
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