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.

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