NLRP3 inflammasome activation in astrocytes restricts SARS-CoV-2 through gasdermin-D-driven IL-1β release.

ABSTRACT: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the third highly pathogenic coronavirus to emerge in humans in recent decades. Although primarily a respiratory virus, SARS-CoV-2 can invade the central nervous system (CNS), leading to severe neurological manifestations such as stroke, encephalopathy, and memory loss. However, the mechanisms by which neural cells control SARS-CoV-2 infection remain poorly understood. Here, we demonstrate that SARS-CoV-2 and its Nucleocapsid (N) and Spike (S) proteins induce classical NLRP3 inflammasome activation in astrocytes. Notably, astrocytes lacking NLRP3 or caspase-1 exhibit higher viral loads, indicating a crucial role of the NLRP3 inflammasome in astrocyte-mediated viral control. Similarly, gasdermin-D (GSDMD)-deficient astrocytes di

SUBMITTER: de Farias IS 

PROVIDER: S-EPMC12864467 | biostudies-literature | 2025

REPOSITORIES: biostudies-literature