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. 2025 Apr 17;188(8):2111-2126.e21.
doi: 10.1016/j.cell.2025.01.033. Epub 2025 Feb 20.

A nucleosome switch primes hepatitis B virus infection

Nicholas A Prescott  1 , Tracy Biaco  2 , Andrés Mansisidor  3 , Yaron Bram  4 , Justin Rendleman  3 , Sarah C Faulkner  5 , Abigail A Lemmon  1 , Christine Lim  4 , Rachel Tiersky  4 , Eralda Salataj  6 , Liliana Garcia-Martinez  7 , Rodrigo L Borges  7 , Lluis Morey  7 , Pierre-Jacques Hamard  6 , Richard P Koche  6 , Viviana I Risca  8 , Robert E Schwartz  9 , Yael David  10
Affiliations

A nucleosome switch primes hepatitis B virus infection

Nicholas A Prescott et al. Cell. .

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.

Keywords: chromatin; epigenetics; hepatitis B virus; nucleosome stability; transcription.

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Conflict of interest statement

Declaration of interests R.E.S. is on the scientific advisory boards of Miromatrix Inc. and Lime Therapeutics and is a speaker and consultant for Alnylam Inc.

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References

    1. Yuen M-F, Chen D-S, Dusheiko GM, Janssen HLA, Lau DTY, Locarnini SA, Peters MG, and Lai C-L (2018). Hepatitis B virus infection. Nature Reviews Disease Primers 4, 18035. 10.1038/nrdp.2018.35. - DOI - PubMed
    1. Levrero M, and Zucman-Rossi J. (2016). Mechanisms of HBV-induced hepatocellular carcinoma. Journal of Hepatology 64, S84–S101. 10.1016/j.jhep.2016.02.021. - DOI - PubMed
    1. Yan H, Zhong G, Xu G, He W, Jing Z, Gao Z, Huang Y, Qi Y, Peng B, Wang H, et al. (2012). Sodium taurocholate cotransporting polypeptide is a functional receptor for human hepatitis B and D virus. eLife 2012, 1–28. 10.7554/eLife.00049. - DOI - PMC - PubMed
    1. Rabe B, Vlachou A, Panté N, Helenius A, and Kann M. (2003). Nuclear import of hepatitis B virus capsids and release of the viral genome. Proceedings of the National Academy of Sciences 100, 9849–9854. 10.1073/pnas.1730940100. - DOI - PMC - PubMed
    1. Yang R, Ko Y-H, Li F, Lokareddy RK, Hou C-FD, Kim C, Klein S, Antolínez S, Marín JF, Pérez-Segura C, et al. (2024). Structural basis for nuclear import of hepatitis B virus (HBV) nucleocapsid core. Science Advances 10, eadi7606. 10.1126/sciadv.adi7606. - DOI - PMC - PubMed

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