Scholarlink

<p>The hepatitis B virus (HBV) is a hepatotropic DNA virus that establishes chronic infections and contributes to liver disease and hepatocellular carcinoma. Although HBV persistence depends on the formation of a nuclear covalently closed circular DNA (cccDNA) minichromosome, the spatial organization of HBV within host chromatin and its impact on host transcriptional and epigenomic landscapes remain poorly understood. In this study, we analyzed the interactions between HBV DNA and host chromatin, the effects of infection on three-dimensional genome organization, and the resulting transcriptional and epigenomic responses. Using an integrated 4C-seq, in situ Hi-C, RNA-seq, and ChIP-seq/CUT&amp;Tag approach in HepG2-hNTCP-C4 cells as well as primary human hepatocytes (PHHs), we quantitatively mapped HBV-interacting regions and assessed their compartmental preferences and associated chromatin states. HBV DNA preferentially localized to gene-rich, transcriptionally active regions enriched in CpG islands, promoters, and gene bodies, without inducing global reorganization of A/B compartments. Host transcriptional and active histone modification profiles remained largely stable, with only subtle and localized changes. In contrast, the viral minichromosome exhibited strong enrichment of H3K4me3 and H3K27ac, indicating an intrinsically active chromatin state. These findings reveal that HBV selectively associates with transcriptionally permissive chromatin while preserving host nuclear architecture, highlighting a fine-tuned balance of “stealth” viral infection that supports productive viral transcription and persistent infection.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Stable state of hepatocyte chromatin during hepatitis B virus infection

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年6月2日

查看全文
  • Daichi Komiyama,
  • Atsushi Okabe,
  • Hirotake Kasai,
  • Masaki Fukuyo,
  • Bahityar Rahmutulla,
  • Koichi Watashi,
  • Kohji Moriishi,
  • Atsushi Kaneda

摘要

The hepatitis B virus (HBV) is a hepatotropic DNA virus that establishes chronic infections and contributes to liver disease and hepatocellular carcinoma. Although HBV persistence depends on the formation of a nuclear covalently closed circular DNA (cccDNA) minichromosome, the spatial organization of HBV within host chromatin and its impact on host transcriptional and epigenomic landscapes remain poorly understood. In this study, we analyzed the interactions between HBV DNA and host chromatin, the effects of infection on three-dimensional genome organization, and the resulting transcriptional and epigenomic responses. Using an integrated 4C-seq, in situ Hi-C, RNA-seq, and ChIP-seq/CUT&Tag approach in HepG2-hNTCP-C4 cells as well as primary human hepatocytes (PHHs), we quantitatively mapped HBV-interacting regions and assessed their compartmental preferences and associated chromatin states. HBV DNA preferentially localized to gene-rich, transcriptionally active regions enriched in CpG islands, promoters, and gene bodies, without inducing global reorganization of A/B compartments. Host transcriptional and active histone modification profiles remained largely stable, with only subtle and localized changes. In contrast, the viral minichromosome exhibited strong enrichment of H3K4me3 and H3K27ac, indicating an intrinsically active chromatin state. These findings reveal that HBV selectively associates with transcriptionally permissive chromatin while preserving host nuclear architecture, highlighting a fine-tuned balance of “stealth” viral infection that supports productive viral transcription and persistent infection.