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Updated: Nov 2, 2025

Identifying Inhibitors of the HBx-DDB1 Interaction Using a Split Luciferase Assay System
Published on: December 21, 2019
SIRT7 restricts HBV transcription and replication through catalyzing desuccinylation of histone H3 associated with
Hai-Bo Yu1, Sheng-Tao Cheng1, Fang Ren1
1The Key Laboratory of Molecular Biology of Infectious Diseases designated by the Chinese Ministry of Education, Chongqing Medical University, Chongqing, China.
Insights
Researchers discovered histone succinylation on hepatitis B virus (HBV) DNA. The enzyme SIRT7 removes this mark, silencing viral transcription and offering a potential new strategy against chronic HBV infection.
Area of Science:
- Epigenetics
- Virology
- Molecular Biology
Background:
- Chronic hepatitis B virus (HBV) infection poses a global health challenge.
- HBV covalently closed circular DNA (cccDNA) persistence is a major barrier to curing chronic hepatitis B (CHB).
- Epigenetic regulation, including histone acetylation and methylation, influences cccDNA transcription.
Purpose of the Study:
- To identify novel histone modifications on the HBV cccDNA minichromosome.
- To investigate the role of SIRT7 in regulating HBV cccDNA transcription.
- To explore potential epigenetic antiviral strategies for CHB.
Main Methods:
- Utilized cccDNA ChIP-Seq to identify histone modifications.
- Investigated the interaction between SIRT7, HBV core protein, and cccDNA.
- Analyzed the cooperative effects of SIRT7 with histone methyltransferases (SUV39H1, SETD2).
Main Results:
- Identified histone succinylation (H3K122succ) as a transcriptionally active modification on cccDNA.
- Demonstrated that SIRT7 desuccinylates H3K122 on cccDNA, interacting with HBV core protein.
- Showed SIRT7, SUV39H1, and SETD2 cooperate to silence HBV transcription via chromatin modulation.
Conclusions:
- Histone succinylation is a newly identified epigenetic mark on HBV cccDNA.
- SIRT7-mediated histone desuccinylation contributes to HBV transcriptional silencing.
- Targeting cccDNA epigenetic modifications, like histone succinylation, presents a promising antiviral approach for CHB.
Abstract:
Chronic hepatitis B virus (HBV) infection is a significant public health burden worldwide. HBV covalently closed circular DNA (cccDNA) organized as a minichromosome in nucleus is responsible for viral persistence and is the key obstacle for a cure of chronic hepatitis B (CHB). Recent studies suggest cccDNA transcription is epigenetically regulated by histone modifications, especially histone acetylation and methylation. In the present study, we identified transcriptionally active histone succinylation (H3K122succ) as a new histone modification on cccDNA minichromosome by using cccDNA ChIP-Seq approach. Silent mating type information regulation 2 homolog 7 (SIRT7), as an NAD+-dependent histone desuccinylase, could bind to cccDNA through interaction with HBV core protein where it catalyzed histone 3 lysine 122 (H3K122) desuccinylation. Moreover, SIRT7 acts cooperatively with histone methyltransferase, suppressor of variegation 3-9 homolog 1 (SUV39H1) and SET domain containing 2 (SETD2) to induce silencing of HBV transcription through modulation of chromatin structure. Our data improved the understanding of histone modifications of the cccDNA minichromosome, thus transcriptional silencing of cccDNA may represent a novel antiviral strategy for the prevention or treatment of HBV infection.
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