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

IF 21.8 1区 医学 Q1 IMMUNOLOGY Cellular &Molecular Immunology Pub Date : 2024-10-08 DOI:10.1038/s41423-024-01221-2
Qiannv Liu, Weitao Li, Yan Qian, Chunlei Wang, Chun Kong, Mengqian Li, Liangliang Sun, Lang Sun, Yanli Pang, Changtao Jiang, Shuo Wang, Pengyan Xia
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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.

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TET3 炎症体感知独特的 HSV-1 长蛋白,以便病毒粒子从细胞核出芽。
炎症体在抵抗各种病原体感染方面发挥着重要作用。HSV-1 是一种在人类中具有高度传染性的病毒。HSV-1 颗粒从细胞核中萌发的过程是疱疹病毒所独有的,但具体机制尚不清楚。在这里,我们筛选了参与 HSV-1 复制的基因。我们发现 TET3 在 HSV-1 感染中扮演着重要角色。TET3能识别HSV-1的UL蛋白,激活后可直接与caspase-1结合,激活细胞核中不依赖于ASC的炎性体。随后,GSDMD 在细胞核中的裂解对 HSV-1 颗粒从细胞核中出芽至关重要。抑制 GSDMD 在核膜上的穿孔能力可以显著减少 HSV-1 的成熟和传播。我们的研究结果可能会为未来治疗HSV-1提供一种新方法。
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来源期刊
CiteScore
31.20
自引率
1.20%
发文量
903
审稿时长
1 months
期刊介绍: Cellular & Molecular Immunology, a monthly journal from the Chinese Society of Immunology and the University of Science and Technology of China, serves as a comprehensive platform covering both basic immunology research and clinical applications. The journal publishes a variety of article types, including Articles, Review Articles, Mini Reviews, and Short Communications, focusing on diverse aspects of cellular and molecular immunology.
期刊最新文献
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