A nucleosome switch primes hepatitis B virus infection Journal Article
| Authors: | Prescott, N. A.; Biaco, T.; Mansisidor, A.; Bram, Y.; Rendleman, J.; Faulkner, S. C.; Lemmon, A. A.; Lim, C.; Tiersky, R.; Salataj, E.; Garcia-Martinez, L.; Borges, R. L.; Morey, L.; Hamard, P. J.; Koche, R. P.; Risca, V. I.; Schwartz, R. E.; David, Y. |
| Article Title: | A nucleosome switch primes hepatitis B virus infection |
| Abstract: | Chronic hepatitis B virus (HBV) infection is an incurable pathogen responsible for causing liver disease and hepatocellular carcinoma. During the genesis of infection, HBV establishes an independent minichromosome consisting of the viral covalently closed circular DNA (cccDNA) genome and host histones. The viral X gene must be expressed immediately upon infection to induce degradation of the host silencing factor, the Smc5/6 complex. However, the relationship between cccDNA chromatinization and X gene transcription remains poorly understood. By establishing a reconstituted viral minichromosome platform, we found that nucleosome occupancy in cccDNA regulates X transcription. We corroborated these findings in situ and further showed that the chromatin-destabilizing molecule CBL137 inhibits full-length X transcription and HBV infection in primary human hepatocytes. Our results shed light on a long-standing paradox and represent a potential therapeutic approach for the treatment of chronic HBV infection. © 2025 Elsevier Inc. |
| Keywords: | controlled study; human cell; hepatitis b; liver cell carcinoma; cell viability; gene expression; genetic transcription; enzyme linked immunosorbent assay; genetic transfection; epigenetics; chromatin; chromatin immunoprecipitation; transcription; plasmid; immunoblotting; liver disease; real time polymerase chain reaction; hepatitis b virus; gel mobility shift assay; virus genome; nucleosome; histone modification; minichromosome maintenance protein 2; atomic force microscopy; minichromosome; capsid protein; circular dna; human; article; chronic hepatitis b; rna sequencing; hela cell line; hek293t cell line; hep-g2 cell line; nucleosome stability; structural maintenance of chromosome protein 1; hepad38 cell line; ihh cell line |
| Journal Title: | Cell |
| Volume: | 188 |
| Issue: | 8 |
| ISSN: | 0092-8674 |
| Publisher: | Cell Press |
| Date Published: | 2025-04-17 |
| Start Page: | 2111 |
| End Page: | 2126.e21 |
| Language: | English |
| DOI: | 10.1016/j.cell.2025.01.033 |
| PUBMED: | 39983728 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | The MSK Cancer Center Support Grant (P30 CA008748) is acknowledged in the PDF. Corresponding MSK author is Yael David -- Source: Scopus |
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