Quercetin protects against murine cytomegalovirus-induced pneumonia via suppression of viral replication and NLRP3 inflammasome activation.

Cytomegalovirus (CMV)-induced pneumonia is associated with excessive pulmonary inflammation and severe lung injury, particularly in immunocompromised individuals. Effective therapeutic strategies targeting both viral replication and inflammation-driven lung damage remain limited. Quercetin, a naturally occurring flavonoid, has been reported to exert anti-inflammatory and antiviral activities. However, its role in CMV-induced pneumonia and the underlying mechanisms remain unclear. In this study, we investigated the protective effects of quercetin in a murine cytomegalovirus (MCMV)-induced pneumonia model established in female BALA/c-nu mice and explored its impact on viral replication and NLRP3 inflammasome activation. Our results showed that quercetin treatment significantly alleviated lung pathological injury, reduced inflammatory cell infiltration, and decreased the production of pro-inflammatory cytokines in MCMV-infected mice. Notably, quercetin also reduced viral replication, as evidenced by decreased MCMV-GFP fluorescence, lower viral titers, and reduced expression of the viral immediate-early gene MIE1 in vivo and in vitro. Mechanistically, quercetin suppressed NLRP3 inflammasome activation, as indicated by reduced expression of NLRP3, cleaved caspase-1, and IL-1β. In vitro studies further confirmed that quercetin inhibited inflammasome activation in macrophages. Collectively, these findings demonstrate that quercetin protects against MCMV-induced pneumonia by suppressing viral replication and NLRP3 inflammasome activation, identifying quercetin as a mechanistic probe and a lead structure for host-directed intervention in virus-induced inflammatory lung disease.