Chen P, Zhao J, Chen NK, Chen ZY. Hepatocyte-intrinsic innate immunity in hepatitis B virus infection: A focused review. World J Hepatol 2025; 17(6): 104533 [DOI: 10.4254/wjh.v17.i6.104533]
Corresponding Author of This Article
Ping Chen, PhD, Department of Research and Development, Syno Minicircle Biotechnology Co. Ltd., A1003, Gaoke Innovation Center, Guangqiao Road, Guangming District, Shenzhen 518107, Guangdong Province, China. pingchen09@gmail.com
Research Domain of This Article
Virology
Article-Type of This Article
Minireviews
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/
Ping Chen, Ning-Kai Chen, Zhi-Ying Chen, Department of Research and Development, Syno Minicircle Biotechnology Co. Ltd., Shenzhen 518107, Guangdong Province, China
Jing Zhao, Scientific Research Center, The Seventh Affiliated Hospital, Sun Yat-Sen University, Shenzhen 518107, Guangdong Province, China
Co-corresponding authors: Ping Chen and Zhi-Ying Chen.
Author contributions: Chen P designed the structure of this review and wrote the manuscript; Chen P, Chen NK and Chen ZY revised the manuscript; Zhao J contributed to the literature collection; All authors read and approved the final manuscript.
Supported by Shenzhen Medical Research Fund, No. D2301010; and Shenzhen Science and Technology Program, No. RCYX20231211090346060.
Conflict-of-interest statement: The authors declare no conflict of interests for this article.
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: Ping Chen, PhD, Department of Research and Development, Syno Minicircle Biotechnology Co. Ltd., A1003, Gaoke Innovation Center, Guangqiao Road, Guangming District, Shenzhen 518107, Guangdong Province, China. pingchen09@gmail.com
Received: December 25, 2024 Revised: April 17, 2025 Accepted: June 4, 2025 Published online: June 27, 2025 Processing time: 183 Days and 3.6 Hours
Abstract
Chronic hepatitis B virus (HBV) infection remains a major health burden worldwide. To establish a persistence infection, HBV needs to evade both adaptive and innate immune surveillance. Multiple mechanisms for adaptive immunity evasion have been established, but how HBV evades the innate surveillance is less clear. There are three types of host cells involving in the innate immune responses against HBV infection: Hepatocytes, hepatic nonparenchymal cells and conventional innate immune cells. Among these, hepatocytes are the only target cells that are susceptible to HBV infection and the only confirmed site where HBV replication takes place. This review focuses on the hepatocyte-intrinsic innate immunity; one of the earliest host defense responses. After entering hepatocytes, the viral components can be sensed by the cellular pattern recognition receptors. This triggers downstream antiviral responses capable of inhibiting viral replication and even degrading the viral DNA genome directly or indirectly. However, HBV has evolved a variety of sophisticated strategies to evade intracellular immune defense, resulting in the establishment of infection. Here, we provide insights into the mechanisms of the intrinsic innate immune response of hepatocytes and how HBV escapes these defense mechanisms. Hopefully, this will lay the foundation for the development of novel anti-HBV therapies.
Core Tip: Despite the advancements in hepatitis B virus (HBV) immunology, the mechanism by which hepatocytes exert their innate immune responses against HBV infection remains poorly understood. This article focused on the complex interplay between hepatocytes and the innate immune response during HBV infection and summarized the recent findings about how HBV evading the innate response to promoter viral persistence. These insights may be helpful for developing novel anti-HBV immune-based therapies.
