Human cytomegalovirus protein US18 promotes NLRP3 inflammasome activation

Human cytomegalovirus (HCMV) infection of monocytes results in inflammatory response by triggering the activation of inflammasomes and subsequent release of inflammatory cytokines including IL-1β and IL-18 and pyroptosis. However, the mechanisms by which HCMV induces inflammatory response remain unclear. Here, we identified that the HCMV protein US18 promotes NLRP3 inflammasome activation, IL-1β release and pyroptosis. US18 associates with the NLRP3 inflammasome components NEK7, NLRP3 and pro-IL-1β, and promotes the oligomerization and speck formation of NLRP3. Knockdown of US18 inhibits HCMV-induced activation of the NLRP3 inflammasome, IL-1β release and pyroptosis. Our findings suggest that HCMV US18 positively regulates activation of the NLRP3 inflammasome and inflammatory response upon HCMV infection.