Xu ZY, Gao JS, He Y, Xiao XQ, Gong GZ, Zhang M. Hepatitis B virus confers innate immunity evasion through hepatitis B virus-miR-3 down-regulation of cGAS-Sting-IFN signaling. World J Hepatol 2025; 17(2): 99292 [DOI: 10.4254/wjh.v17.i2.99292]
Corresponding Author of This Article
Guo-Zhong Gong, MD, Doctor, Department of Infectious Diseases, The Second Xiangya Hospital, Central South University, No. 139 Renmin Middle Road, Changsha 410011, Hunan Province, China. gongguozhong@csu.edu.cn
Research Domain of This Article
Infectious Diseases
Article-Type of This Article
Basic Study
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Zhen-Yu Xu, Jia-Shi Gao, Ying He, Xin-Qiang Xiao, Guo-Zhong Gong, Department of Infectious Diseases, The Second Xiangya Hospital, Central South University, Changsha 410011, Hunan Province, China
Min Zhang, Institute of Hepatology and Department of Infectious Diseases, The Second Xiangya Hospital, Central South University, Changsha 410011, Hunan Province, China
Co-corresponding authors: Guo-Zhong Gong and Min Zhang.
Author contributions: Gong GZ and Zhang M contribute equally to this study as co-corresponding authors; Xu ZY and Gao JS collected data and drafted the manuscript; He Y and Xiao XQ contributed to the interpretation of the data, and the critical revision of the manuscript; Zhang M, Gong GZ supervised the study; Gong GZ designed the study and revised the manuscript; all authors approved the final version of the manuscript.
Supported by National Natural Science Foundation of China, Key Project, No. 82430071; The Scientific Research Program of FuRong Laboratory, No. 2023SK2108; Clinical Medical Research Center for Viral Hepatitis of Hunan Province, No. 2023SK4009; Hunan Provincial Natural Science Foundation, No. 2023JJ60440; and Hunan Provincial Health Commission Research Program, No. C202303088786.
Institutional review board statement: This study did not involve human subjects.
Conflict-of-interest statement: The authors declare no conflicts of interest.
Data sharing statement: Data supporting the findings of this study are available upon reasonable request from the corresponding author.
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Guo-Zhong Gong, MD, Doctor, Department of Infectious Diseases, The Second Xiangya Hospital, Central South University, No. 139 Renmin Middle Road, Changsha 410011, Hunan Province, China. gongguozhong@csu.edu.cn
Received: July 19, 2024 Revised: December 5, 2024 Accepted: January 18, 2025 Published online: February 27, 2025 Processing time: 216 Days and 7.3 Hours
Abstract
BACKGROUND
Hepatitis B virus (HBV) evades the innate immunity and leads to persistent chronic infection, but the molecular mechanism is still not well known.
AIM
To investigate whether HBV-miR-3 is involved in HBV immune evasion.
METHODS
HBV-miR-3 agomir and antagomir were employed to verify the effectiveness of HBV-miR-3 on cGAS-Sting-IFN pathway through the experiments on relative luciferase activity, cGAS protein expression, Sting phosphorylation and interferon (IFN) production.
RESULTS
HBV-miR-3 down-regulates cGAS protein expression post-transcriptionally by inhibition of cGAS 3’-untranslated region (3’-UTR) activity, which results in lower Sting phosphorylation and IFN production. HBV-miR-3 antagomir rescued cGAS protein expression, Sting phosphorylation and IFN-β production.
CONCLUSION
HBV-miR-3 plays an important role in HBV immunity evasion by targeting cGAS 3’-UTR and interfering with cGAS-Sting-IFN pathway.
Core Tip: This study uncovers a novel mechanism of hepatitis B virus (HBV) immunity evasion through HBV-miR-3, a recently identified HBV-encoded microRNA. HBV-miR-3 down-regulates the cGAS-STING-IFN pathway by inhibiting cGAS 3’ untranslated region activity, leading to decreased cGAS protein expression, STING phosphorylation, and interferon production. The findings highlight the crucial role of HBV-miR-3 in modulating host immune responses, providing insights into potential therapeutic targets for HBV infection.
