Department of Immunology, School of Basic Medical Sciences, Peking University, Beijing, 100191, China.
NHC Key Laboratory of Medical Immunology, Peking University, Beijing, 100191, China.
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。
