Int J Biol Sci 2020; 16(15):2924-2937. doi:10.7150/ijbs.50074

Research Paper

HPV E7 inhibits cell pyroptosis by promoting TRIM21-mediated degradation and ubiquitination of the IFI16 inflammasome

Yinjing Song1*, Xia Wu1*, Yaohan Xu1*, Jiang Zhu1, Jiaying Li2, Ziqi Zou2, Luxia Chen1, Boya Zhang1, Chunting Hua1, Han Rui1, Qiaoli Zheng1, Qiang Zhou1✉, Qingqing Wang2✉, Hao Cheng1✉

1. Department of Dermatology and Venereology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou 310016, Zhejiang, PR China.
2. Institute of Immunology, Zhejiang University School of Medicine, Hangzhou 310058, China.
*These authors contributed equally to this work.

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Citation:
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. HPV E7 inhibits cell pyroptosis by promoting TRIM21-mediated degradation and ubiquitination of the IFI16 inflammasome. Int J Biol Sci 2020; 16(15):2924-2937. doi:10.7150/ijbs.50074. Available from http://www.ijbs.com/v16p2924.htm

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Abstract

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.

Keywords: Human papillomavirus E7, pyroptosis, ubiquitination, inflammasome