HPV E7 inhibits cell pyroptosis by promoting TRIM21-mediated degradation and ubiquitination of the IFI16 inflammasome.
HPV E7 inhibits cell pyroptosis by promoting TRIM21-mediated degradation and ubiquitination of the IFI16 inflammasome.
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HPV E7 通过促进 TRIM21 介导的 IFI16 炎性体降解和泛素化来抑制细胞焦亡
DOI：
10.7150/ijbs.50074
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发表时间：
2020
影响因子：
9.2
通讯作者：
Cheng H
中科院分区：
文献类型：
--
作者：
Song Y;Wu X;Xu Y;Zhu J;Li J;Zou Z;Chen L;Zhang B;Hua C;Rui H;Zheng Q;Zhou Q;Wang Q;Cheng H
人乳头瘤病毒（HPV）是一种DNA病毒，可引起性传播感染。HPV癌蛋白E7在调节宿主免疫中起关键作用，促进HPV的免疫逃逸和宫颈癌或生殖器疣的发生。细胞凋亡是一种高度炎症性的细胞程序性死亡形式，可由炎性小体诱导并作为对病原性感染的防御。然而，HPV E7是否可以调节细胞凋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dsDNA转染诱导的细胞凋亡。HPVE7还能抑制炎性小体的活化以及IL-18和IL-1 β的产生。质谱和免疫沉淀显示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炎性小体，导致细胞焦亡的抑制和免疫监视的自我逃避。因此，我们的研究揭示了HPV感染中重要的免疫逃逸机制，并可能为开发新的免疫策略以有效恢复抗病毒免疫提供靶点。
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.
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