REVIEW article
Front. Immunol.
Sec. Viral Immunology
This article is part of the Research TopicHost factors in hepatitis B virus: Mechanistic insights and implications for interferon therapyView all 4 articles
HBc: The Multifunctional Architect of HBV Replication, Immune Evasion, and Therapeutic Innovation
Provisionally accepted
- Institute of Translational Medicine, The First Hospital of Jilin University, Changchun, China
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The hepatitis B core protein (HBc) is a multifunctional viral protein central to hepatitis B virus (HBV) replication, immune modulation, and capsid assembly. Structurally, HBc consists of an N-terminal domain (NTD) essential for capsid formation and a C-terminal domain (CTD) critical for RNA binding and genome packaging. Frequent HBc mutations, driven by HBV's high mutation rate, enhance the virus's ability to adapt to environmental pressures. HBc interacts with host factors to regulate viral transcription, stabilize capsids, and modulate immune responses, including the suppression of interferon signaling and promotion of immune exhaustion. Clinically, anti-HBc antibodies serve as key diagnostic markers, while HBc-targeting therapies, such as capsid assembly modulators (CAMs), represent promising strategies for achieving functional cure. This review uniquely integrates structural, functional, and clinical perspectives on HBc, providing a comprehensive understanding of its role in HBV biology and its potential as a therapeutic target. By highlighting recent advances in CAMs and the challenges of drug resistance, this work offers valuable insights for researchers and clinicians aiming to develop innovative HBV treatments.
Keywords: Hepatitis B core protein (HBc), HBV Replication, Immune Evasion, Capsidassembly modulators (CAMs), Therapeutic target
Received: 02 Jul 2025; Accepted: 28 Oct 2025.
Copyright: © 2025 Tan, Zhu, Song, Xu and Huang. 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: Guangyun Tan, tgy0425@jlu.edu.cn
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