Rotavirus NSP1 activates human NLRP1 inflammasome

Rotavirus infection robustly activates the human NLRP1 inflammasome, with NSP1 triggering activation through p38 MAPK-dependent and -independent pathways in reconstituted cell lines.

• Why it matters: Enteric viruses can activate inflammasomes, but the specific viral components and mechanisms that engage human NLRP1 remain incompletely defined.
• What they did: Using NLRP1-reconstituted cell lines and reverse genetics-rescued recombinant rotaviruses, NSP1 activated NLRP1 inflammasome signaling in the absence of double-stranded RNA; the NSP1 C-terminus was essential, while the C-terminal IRF3-binding site was not.
• The result: NSP1 induced proteasomal degradation of NLRP1 to elicit activation, requiring host neddylation and the Cullin-3/Elongin B/C ubiquitin ligase complex, suggesting RV engages parallel NLRP1 surveillance pathways.