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
  • 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. [email protected].
  • 9. Department of Immunology, School of Basic Medical Sciences, Peking University, Beijing, 100191, China. [email protected].
  • 10. NHC Key Laboratory of Medical Immunology, Peking University, Beijing, 100191, China. [email protected].
  • 11. Key Laboratory of Molecular Immunology, Chinese Academy of Medical Sciences, Beijing, 100191, China. [email protected].
  • # 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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