bioRxiv : the preprint server for biology · 2024
A nucleosome switch primes Hepatitis B Virus infection.
СтатьяПрепринтНазвание и аннотация: Перевод в очереди
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Prescott Nicholas A, Mansisidor Andrés, Bram Yaron, Biaco Tracy, Rendleman Justin, Faulkner Sarah C, Lemmon Abigail A, Lim Christine, Hamard Pierre-Jacques, Koche Richard P, Risca Viviana I, Schwartz Robert E, David Yael
Аннотация
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.