A nucleosome switch primes Hepatitis B Virus infection.

Autor:	Prescott NA; Tri-Institutional PhD Program in Chemical Biology; New York, NY 10065, USA.; Chemical Biology Program, Memorial Sloan Kettering Cancer Center; New York, NY 10065, USA., Mansisidor A; Laboratory of Genome Architecture and Dynamics, The Rockefeller University; New York, NY 10065, USA.; These authors contributed equally., Bram Y; Division of Gastroenterology & Hepatology, Department of Medicine, Weill Cornell Medicine; New York, NY 10065, USA.; These authors contributed equally., Biaco T; Chemical Biology Program, Memorial Sloan Kettering Cancer Center; New York, NY 10065, USA.; Department of Pharmacology, Weill Cornell Medicine; New York, NY 10065, USA.; These authors contributed equally., Rendleman J; Laboratory of Genome Architecture and Dynamics, The Rockefeller University; New York, NY 10065, USA., Faulkner SC; Chemical Biology Program, Memorial Sloan Kettering Cancer Center; New York, NY 10065, USA., Lemmon AA; Tri-Institutional PhD Program in Chemical Biology; New York, NY 10065, USA.; Chemical Biology Program, Memorial Sloan Kettering Cancer Center; New York, NY 10065, USA., Lim C; Division of Gastroenterology & Hepatology, Department of Medicine, Weill Cornell Medicine; New York, NY 10065, USA., Hamard PJ; Epigenetics Research Innovation Lab, Center for Epigenetics Research, Memorial Sloan Kettering Cancer Center; New York, NY 10065, USA., Koche RP; Epigenetics Research Innovation Lab, Center for Epigenetics Research, Memorial Sloan Kettering Cancer Center; New York, NY 10065, USA., Risca VI; Laboratory of Genome Architecture and Dynamics, The Rockefeller University; New York, NY 10065, USA., Schwartz RE; Division of Gastroenterology & Hepatology, Department of Medicine, Weill Cornell Medicine; New York, NY 10065, USA.; Department of Physiology and Biophysics, Weill Cornell Medicine; New York, NY 10065, USA., David Y; Tri-Institutional PhD Program in Chemical Biology; New York, NY 10065, USA.; Chemical Biology Program, Memorial Sloan Kettering Cancer Center; New York, NY 10065, USA.; Department of Pharmacology, Weill Cornell Medicine; New York, NY 10065, USA.; Lead Contact.
Jazyk:	angličtina
Zdroj:	BioRxiv : the preprint server for biology [bioRxiv] 2024 Jun 12. Date of Electronic Publication: 2024 Jun 12.
DOI:	10.1101/2023.03.03.531011
Abstrakt:	Chronic hepatitis B virus (HBV) infection is an incurable global health threat 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, Smc5/6. However, the relationship between cccDNA chromatinization and X gene transcription remains poorly understood. Establishing a reconstituted viral minichromosome platform, we found that nucleosome occupancy in cccDNA drives X transcription. We corroborated these findings in cells and further showed that the chromatin destabilizing molecule CBL137 inhibits X transcription and HBV infection in hepatocytes. Our results shed light on a long-standing paradox and represent a potential new therapeutic avenue for the treatment of chronic HBV infection. Competing Interests: 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. All other authors declare that they have no competing interests.
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu