Human papillomavirus (HPV) is a DNA virus that causes sexually transmitted infections. The HPV oncoprotein E7 plays a critical role in the regulation of host immunity to promote the immune escape of HPV and the occurrence of cervical cancer or genital warts. Pyroptosis, a highly inflammatory form of programmed cell death, can be induced by inflammasomes and acts as a defense against pathogenic infection. However, whether HPV E7 can regulate cell pyroptosis to evade immune surveillance has not been determined. In this study, we found that HPV E7 could inhibit cell pyroptosis induced by transfection with dsDNA. The activation of the inflammasome, and the production of IL-18 and IL-1β were also restrained by HPV E7. Mass spectrometry and immunoprecipitation showed that HPV E7 interacted with IFI16 and TRIM21. We also discovered that HPV E7 recruited the E3 ligase TRIM21 to ubiquitinate and degrade the IFI16 inflammasome, leading to the inhibition of cell pyroptosis and self-escape from immune surveillance. Thus, our study reveals an important immune escape mechanism in HPV infection and may provide targets for the development of a novel immunotherapeutic strategy to effectively restore antiviral immunity.

中文翻译：

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HPV E7通过促进TRIM21介导的IFI16炎性体降解和泛素化抑制细胞焦亡

人乳头瘤病毒 (HPV) 是一种导致性传播感染的 DNA 病毒。HPV癌蛋白E7在调节宿主免疫以促进HPV的免疫逃逸和宫颈癌或尖锐湿疣的发生中起关键作用。Pyroptosis 是一种高度炎症性的程序性细胞死亡形式，可由炎症小体诱导，并作为对病原体感染的防御。然而，HPV E7是否可以调节细胞焦亡以逃避免疫监视尚未确定。在本研究中，我们发现 HPV E7 可以抑制转染 dsDNA 诱导的细胞焦亡。炎症小体的激活以及 IL-18 和 IL-1β 的产生也受到 HPV E7 的抑制。质谱和免疫沉淀表明 HPV E7 与 IFI16 和 TRIM21 相互作用。我们还发现 HPV E7 募集 E3 连接酶 TRIM21 来泛素化和降解 IFI16 炎性体，从而抑制细胞焦亡和自我逃避免疫监视。因此，我们的研究揭示了 HPV 感染中重要的免疫逃逸机制，并可能为开发一种有效恢复抗病毒免疫的新型免疫治疗策略提供靶点。