TET3 炎性小体感知独特的长 HSV-1 蛋白，以促进病毒粒子从核内出芽。
The TET3 inflammasome senses unique long HSV-1 proteins for virus particle budding from the nucleus.
机构信息
Department of Immunology, School of Basic Medical Sciences, Peking University, Beijing, 100191, China.
NHC Key Laboratory of Medical Immunology, Peking University, Beijing, 100191, China.
出版信息
Cell Mol Immunol. 2024 Nov;21(11):1322-1334. doi: 10.1038/s41423-024-01221-2. Epub 2024 Oct 8.
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.
炎性小体在抵抗各种病原体引起的感染中发挥着重要作用。HSV-1 是一种在人类中高度传染的病毒。HSV-1 颗粒从细胞核出芽的过程是单纯疱疹病毒所特有的，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 感染中起着至关重要的作用。TET3 识别 HSV-1 的 UL 蛋白，在被激活后，它可以直接与 caspase-1 结合，在细胞核中激活一种 ASC 非依赖性炎性小体。随后在细胞核中对 GSDMD 的切割对于 HSV-1 颗粒从细胞核出芽至关重要。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为未来 HSV-1 的治疗提供一种新的方法。
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