2. Academic Validation
  3. Human cytomegalovirus protein US18 promotes NLRP3 inflammasome activation

Human cytomegalovirus protein US18 promotes NLRP3 inflammasome activation

  • Biochem Biophys Res Commun. 2025 Aug 15:775:152110. doi: 10.1016/j.bbrc.2025.152110.
Yu Zhang 1,  Ya-Li Lei 2,  Peng Ren 2,  Xin-Mei Yang 2,  Jun-Hui Song 2,  Shu Li 2,  Chun-Yu Zhu 3,  Xue-Mei Yi 4
Affiliations

Affiliations

  • 1 College of Life Sciences, Liaoning University, Shenyang, China; Department of Infectious Diseases, Frontier Science Center for Immunology and Metabolism, Medical Research Institute, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan, China.
  • 2 Department of Infectious Diseases, Frontier Science Center for Immunology and Metabolism, Medical Research Institute, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan, China.
  • 3 College of Life Sciences, Liaoning University, Shenyang, China. Electronic address: zhuchunyu@lnu.edu.cn.
  • 4 Department of Infectious Diseases, Frontier Science Center for Immunology and Metabolism, Medical Research Institute, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan, China. Electronic address: xuemeiyi@whu.edu.cn.
PMID: 40450990 DOI: 10.1016/j.bbrc.2025.152110
Abstract

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.

Keywords

Human cytomegalovirus; NLRP3 inflammasome; Pyroptosis; US18.

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