Related Experiment Video
Updated: May 10, 2026
Stem Cell-Derived Viral Ag-Specific T Lymphocytes Suppress HBV Replication in Mice
Published on: September 25, 2019
HBx-induced HSPB1 is a potential therapeutic target owing to its modulation of HBV cccDNA and hepatic immune
Hongfeng Yuan1, Lina Zhao1, Guang Yang1
1State Key Laboratory of Druggability Evaluation and Systematic Translational Medicine, Tianjin Key Laboratory of Digestive Cancer, Department of Gastrointestinal Cancer Biology, Tianjin Cancer Institute, Liver Cancer Center, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer, Tianjin 300060, China.
Background & Aims:
Chronic infection with HBV remains a significant public health concern, and current therapies are inadequate. Here, we report that HBx-elevated heat shock protein B1 (HSPB1) contributes to the regulation of HBV covalently closed circular DNA (cccDNA) and hepatic immune responses.
Methods:
Molecular and cellular in vitro assays were employed to investigate the effects and underlying mechanisms of HSPB1 on HBV cccDNA and HBV replication in HBV-infected cells. The antiviral efficacy of candidate agents targeting cccDNA and the immune response was assessed in HBV-infected cells, human liver chimeric mice, and hydrodynamic injection-based HBV-persistent immunocompetent C57BL/6 mice.
Results:
HSPB1 enhanced cccDNA stability by reducing the recruitment and binding of APOBEC3A/APOBEC3B to cccDNA. Interaction with HBx increased cellular HSPB1 levels by decreasing its ubiquitination, while enhanced phosphorylation promoted nuclear accumulation of HSPB1. Therapeutically, we developed a peptide, D-TK, derived from the HBXIP peptide sequence that targets HBx and limits cccDNA by blocking the interaction between HSPB1 and HBx, ultimately resulting in reduced HBV replication. Nobly, D-TK reduced the frequency of regulatory T cells and enhanced the frequency and activity of CD8+ T cells through HSPB1, thereby contributing to suppression of HBV replication.
Conclusions:
HSPB1 represents a novel therapeutic target by modulating HBV cccDNA and immune responses in the liver. By suppressing cccDNA and enhancing immune responses, D-TK represents a promising therapeutic candidate for HBV treatment.
Impact And Implications:
Chronic infection with HBV remains a significant global health concern, and current therapeutic options are inadequate. In this study, we demonstrate that HBV X protein (HBx)-induced elevation of HSPB1 contributes to the regulation of HBV covalently closed circular DNA (cccDNA) and hepatic immune responses. We engineered a peptide, D-TK, that targets HBx, effectively suppresses cccDNA, and activates immune responses through HSPB1. Our findings offer new insights into the mechanism by which HBx-induced HSPB1 modulates HBV cccDNA and immune regulation in the liver.
More Related Videos
05:55Identifying Inhibitors of the HBx-DDB1 Interaction Using a Split Luciferase Assay System
Published on: December 21, 2019
11:34A Competent Hepatocyte Model Examining Hepatitis B Virus Entry through Sodium Taurocholate Cotransporting Polypeptide as a Therapeutic Target
Published on: May 10, 2022
