Sorbonne Université, INSERM, Centre de Recherche Saint-Antoine, F-75012, Paris, France.
Antiviral Res. 2023 Sep;217:105699. doi: 10.1016/j.antiviral.2023.105699. Epub 2023 Aug 6.
Epstein-Barr virus (EBV) is a highly prevalent human herpesvirus that persists for life in more than 95% of the adult population. EBV usually establishes an asymptomatic life-long infection, but it is also associated with malignancies affecting B lymphocytes and epithelial cells mainly. The virus alternates between a latent phase and a lytic phase, both of which contribute to the initiation of the tumor process. So far, there is only a limited number of antiviral molecules against the lytic phase, most of them targeting viral replication. Recent studies provided evidence that EBV uses components of the NLRP3 inflammasome to enter the productive phase of its cycle following activation in response to various stimuli. In the present work, we demonstrate that shikonin, a natural molecule with low toxicity which is known to inhibit inflammasome, can efficiently repress EBV reactivation. Similar results were obtained with apigenin and OLT 1177, two other NLRP3 inflammasome inhibitors. It is shown herein that shikonin repressed the transcription of reactivation-induced NLRP3 thereby inhibiting inflammasome activation and EBV lytic phase induction.
EB 病毒（EBV）是一种高度流行的人类疱疹病毒，超过 95%的成年人终身携带。EBV 通常建立无症状的终身感染，但它也与主要影响 B 淋巴细胞和上皮细胞的恶性肿瘤有关。病毒在潜伏期和裂解期之间交替，两者都有助于肿瘤过程的启动。到目前为止，只有少数针对裂解期的抗病毒分子，其中大多数针对病毒复制。最近的研究提供了证据表明，EBV 在响应各种刺激而被激活后，利用 NLRP3 炎症小体的成分进入其周期的产生活性期。在本工作中，我们证明了紫草素是一种毒性低的天然分子，已知它可以抑制炎症小体，能够有效地抑制 EBV 的再激活。紫草素与另两种 NLRP3 炎症小体抑制剂芹菜素和 OLT1177 得到了类似的结果。本文表明，紫草素抑制了再激活诱导的 NLRP3 的转录，从而抑制了炎症小体的激活和 EBV 裂解期的诱导。
