Ansari N, Twohig P. Silent sabotage: How hepatitis B virus-miR-3 disarms innate immunity through cGAS-STING suppression. World J Hepatol 2025; 17(6): 106493 [DOI: 10.4254/wjh.v17.i6.106493]
Corresponding Author of This Article
Patrick Twohig, Assistant Professor, FRCPC, Department of Gastroenterology and Hepatology, University of Rochester Medical Center, 601 Elmwood Avenue, Rochester, NY 14682, United States. patrick_twohig@urmc.rochester.edu
Research Domain of This Article
Gastroenterology & Hepatology
Article-Type of This Article
Letter to the Editor
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/
World J Hepatol. Jun 27, 2025; 17(6): 106493 Published online Jun 27, 2025. doi: 10.4254/wjh.v17.i6.106493
Silent sabotage: How hepatitis B virus-miR-3 disarms innate immunity through cGAS-STING suppression
Nida Ansari, Patrick Twohig
Nida Ansari, Department of Internal Medicine, St. Joseph’s University Medical Center, Paterson, NJ 07504, United States
Patrick Twohig, Division of Gastroenterology and Hepatology, University of Rochester Medical Center, Rochester, NY 14682, United States
Author contributions: Twohig P designed the overall concept and outline of the manuscript; Ansari N contributed to the discussion and design of the manuscript. Ansari N and Twohig P both contributed to the writing, editing of the manuscript, and review of the literature.
Conflict-of-interest statement: The authors report no conflicts of interest.
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: Patrick Twohig, Assistant Professor, FRCPC, Department of Gastroenterology and Hepatology, University of Rochester Medical Center, 601 Elmwood Avenue, Rochester, NY 14682, United States. patrick_twohig@urmc.rochester.edu
Received: February 27, 2025 Revised: March 30, 2025 Accepted: April 23, 2025 Published online: June 27, 2025 Processing time: 118 Days and 9.1 Hours
Abstract
In this editorial, we comment on the article by Xu et al published in the recent issue of the World Journal of Hepatology. The hepatitis B virus (HBV) has evolved sophisticated mechanisms to evade host innate immunity, a hallmark of its persistent infections. This study highlights a pivotal role for HBV-encoded microRNA, specifically HBV-miR-3, in undermining the cyclic GMP-AMP synthase (cGAS)- stimulator of interferon genes (STING)-IFN signaling axis. This pathway is critical for recognizing viral DNA and subsequent production of type I interferons, key antiviral cytokines. HBV-miR-3 achieves this immune evasion by directly downregulating the expression of cGAS, an essential DNA sensor, and STING, its downstream adaptor. By silencing these components, HBV-miR-3 disrupts the activation of downstream interferon regulatory factor 3 and Nuclear Factor Kappa-light-chain-enhancer of Activated B Cells transcription factors, thereby blunting interferon beta production and antiviral gene expression. This strategy allows HBV to persist in hepatocytes by dampening innate immune responses and contributes to immune tolerance, fostering chronic infection. Understanding the role of HBV-miR-3 provides novel insights into HBV pathogenesis and identifies potential therapeutic targets to restore antiviral immunity. Targeting HBV-miR-3 or reactivating the cGAS-STING-IFN pathway could offer promising strategies to counteract HBV immune evasion and resolve chronic infection.
Core Tip: Hepatitis B virus (HBV) evades innate immunity through HBV-miR-3, which suppresses the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING)-IFN pathway, a critical antiviral defense mechanism. By downregulating cGAS and STING, HBV prevents interferon production, allowing the virus to persist and promoting chronic infection. Targeting HBV-miR-3 or restoring this immune pathway could offer new therapeutic strategies to enhance antiviral immunity and combat HBV-related diseases.
