Viruses activate inflammasomes but then subvert resulting inflammatory responses to avoid elimination. We asked whether viruses could instead use such activated or primed inflammasomes to directly aid their propagation and spread. Since herpesviruses are experts at coopting cellular functions, we investigated whether Epstein-Barr virus (EBV), an oncoherpesvirus, exploits inflammasomes to activate its replicative or lytic phase. Indeed, our experiments reveal that EBV exploits several inflammasome sensors to actually activate its replicative phase from quiescence/latency. In particular, TXNIP, a key inflammasome intermediary, causes assembly of the NLRP3 inflammasome, resulting in caspase-1-mediated depletion of the heterochromatin-inducing epigenetic repressor KAP1/TRIM28 in a subpopulation of cells. As a result, only TXNIPhiKAP1lo cells, that is, in a primed/prolytic state, turn expression of the replication/lytic/reactivation switch protein on to enter the replicative phase. Our findings 1) demonstrate that EBV dovetails its escape strategy to a key cellular danger-sensing mechanism, 2) indicate that transcription may be regulated by KAP1 abundance aside from canonical regulation through its posttranslational modification, 3) mechanistically link diabetes, which frequently activates the NLRP3 inflammasome, to deregulation of a tumor virus, and 4) demonstrate that B lymphocytes from NOMID (neonatal onset multisystem inflammatory disease) patients who have NLRP3 mutations and suffer from hyperactive innate responses are defective in controlling a herpesvirus.

中文翻译：

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混杂的炎性体会引发常见肿瘤病毒的复制。


病毒激活炎症小体，但随后破坏产生的炎症反应以避免消除。我们询问病毒是否可以使用这种激活或引发的炎症小体来直接帮助其繁殖和传播。由于疱疹病毒是协调细胞功能的专家，我们研究了 Epstein-Barr 病毒 (EBV)（一种癌疱疹病毒）是否利用炎症小体来激活其复制或裂解阶段。事实上，我们的实验表明 EBV 利用多个炎性体传感器来实际激活其从静止/潜伏期的复制阶段。特别是，TXNIP（一种关键的炎症小体中介物）会引起 NLRP3 炎症小体的组装，从而导致细胞亚群中 caspase-1 介导的异染色质诱导表观遗传阻遏蛋白 KAP1/TRIM28 的消耗。因此，只有 TXNIPhiKAP1lo 细胞，即处于引发/裂解状态的细胞，才会开启复制/裂解/重新激活开关蛋白的表达，从而进入复制期。我们的研究结果 1) 表明 EBV 的逃逸策略与关键的细胞危险感知机制相吻合，2) 表明除了通过其翻译后修饰进行规范调节之外，转录还可能受到 KAP1 丰度的调节，3) 在机制上与糖尿病相关，糖尿病经常激活NLRP3 炎症小体对肿瘤病毒的失调，4) 证明来自 NOMID（新生儿多系统炎症性疾病）患者的 B 淋巴细胞具有 NLRP3 突变并患有过度活跃的先天反应，在控制疱疹病毒方面存在缺陷。