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ORIGINAL RESEARCH article
Front. Immunol.
Sec. Viral Immunology
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1549766
This article is part of the Research TopicHost Dynamics and Immune Evasion: Delineating the Influence of RNA and DNA VirusesView all 4 articles
Human Papillomavirus E1 Proteins Inhibit RIG-I/MDA5-MAVS, TLR3-TRIF, cGAS-STING, and JAK-STAT Signaling Pathways to Evade Innate Antiviral Immunity
Provisionally accepted
Prof. Pei-Hui Wang*
Jinxin Li
Jing Zhang
Cheng-Hao LiYun-Fang Li
Hui-Min ChenTao Li
Qing ZhangBeihua Kong- Shandong University, Jinan, China
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Human papillomavirus (HPV) is a major etiological agent of both malignant and benign lesions, with high-risk types, such as HPV16 and HPV18, being strongly linked to cervical cancer, while low-risk types like HPV11 are associated with benign conditions.While viral proteins such as E6 and E7 are well-established regulators of immune evasion, the role of E1 in modulating the host antiviral responses remains insufficiently characterized. This study investigates the immunomodulatory functions of HPV16 and HPV11 E1 in suppressing innate antiviral immune signaling pathways. Through a combination of RT-qPCR and luciferase reporter assays, we demonstrate that E1 suppresses the production of interferons and interferon-stimulated genes triggered by viral infections and the activation of RIG-I/MDA5-MAVS, TLR3-TRIF, cGAS-STING, and JAK-STAT pathways. Co-immunoprecipitation assays reveal that E1 interacts directly with key signaling molecules within these pathways. E1 also impairs TBK1 and IRF3 phosphorylation and obstructs the nuclear translocation of IRF3, thereby broadly suppressing IFN responses. Additionally, E1 disrupts the JAK-STAT pathway by binding STAT1, which prevents the assembly and nuclear localization of the ISGF3 complex containing STAT1, STAT2, and IRF9, thereby further diminishing antiviral response. These findings establish E1 as a pivotal regulator of immune evasion and suggest its potential as a novel therapeutic target to enhance antiviral immunity in HPVassociated diseases.
Keywords: HPV E1, innate immunity, RIG-I/MDA5-MAVS, cGAS-STING, jak-stat, Immune Evasion, interferon
Received: 21 Dec 2024; Accepted: 25 Mar 2025.
Copyright: © 2025 Wang, Li, Zhang, Li, Li, Chen, Li, Zhang and Kong. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Prof. Pei-Hui Wang, Shandong University, Jinan, China
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