2. Academic Validation
  3. The TET3 inflammasome senses unique long HSV-1 proteins for virus particle budding from the nucleus

The TET3 inflammasome senses unique long HSV-1 proteins for virus particle budding from the nucleus

  • Cell Mol Immunol. 2024 Nov;21(11):1322-1334. doi: 10.1038/s41423-024-01221-2.
Qiannv Liu # 1 2 3,  Weitao Li # 1 2 3,  Yan Qian 1 2 3,  Chunlei Wang 1 2 3,  Chun Kong 1 2 3,  Mengqian Li 1 2 3,  Liangliang Sun 1 2 3,  Lang Sun 1 2 3,  Yanli Pang 4 5,  Changtao Jiang 1 2 6 7,  Shuo Wang 8,  Pengyan Xia 9 10 11
Affiliations

Affiliations

  • 1 Department of Immunology, School of Basic Medical Sciences, Peking University, Beijing, 100191, China.
  • 2 NHC Key Laboratory of Medical Immunology, Peking University, Beijing, 100191, China.
  • 3 Key Laboratory of Molecular Immunology, Chinese Academy of Medical Sciences, Beijing, 100191, China.
  • 4 State Key Laboratory of Female Fertility Preservation, Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing, 100191, China.
  • 5 National Clinical Research Center for Obstetrics and Gynecology, Peking University Third Hospital, Beijing, 100191, China.
  • 6 Department of Physiology and Pathophysiology, School of Basic Medical Sciences, State Key Laboratory of Vascular Homeostasis and Remodeling, Peking University, Beijing, 100191, China.
  • 7 Center for Obesity and Metabolic Disease Research, School of Basic Medical Sciences, Peking University, Beijing, 100191, China.
  • 8 CAS Key Laboratory of Pathogen Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, 100101, Beijing, China. wangshuo@im.ac.cn.
  • 9 Department of Immunology, School of Basic Medical Sciences, Peking University, Beijing, 100191, China. xiap@pku.edu.cn.
  • 10 NHC Key Laboratory of Medical Immunology, Peking University, Beijing, 100191, China. xiap@pku.edu.cn.
  • 11 Key Laboratory of Molecular Immunology, Chinese Academy of Medical Sciences, Beijing, 100191, China. xiap@pku.edu.cn.
  • # Contributed equally.
PMID: 39379602 DOI: 10.1038/s41423-024-01221-2
Abstract

Inflammasomes play important roles in resisting infections caused by various pathogens. HSV-1 is a highly contagious virus among humans. The process by which HSV-1 particles bud from the nucleus is unique to herpes viruses, but the specific mechanism is still unclear. Here, we screened genes involved in HSV-1 replication. We found that TET3 plays an essential role in HSV-1 Infection. TET3 recognizes the UL proteins of HSV-1 and, upon activation, can directly bind to Caspase-1 to activate an ASC-independent inflammasome in the nucleus. The subsequent cleavage of GSDMD in the nucleus is crucial for the budding of HSV-1 particles from the nucleus. Inhibiting the perforation ability of GSDMD on the nuclear membrane can significantly reduce the maturation and spread of HSV-1. Our results may provide a new approach for the treatment of HSV-1 in the future.

Keywords

ASC-independent inflammasome; HSV-1; TET3; unique long proteins.

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