Nicholas A Prescott, Andrés Mansisidor, Yaron Bram, Tracy Biaco, Justin Rendleman, Sarah C Faulkner, Abigail A Lemmon, Christine Lim, Pierre-Jacques Hamard, Richard P Koche, Viviana I Risca, Robert E Schwartz, Yael David
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引用次数: 0
摘要
慢性乙型肝炎病毒（HBV）感染是一种无法治愈的全球性健康威胁，可导致肝病和肝细胞癌。在感染发生过程中，HBV 会建立一个独立的小染色体，由病毒共价闭合环状 DNA（cccDNA）基因组和宿主组蛋白组成。病毒 X 基因必须在感染后立即表达，以诱导宿主沉默因子 Smc5/6 的降解。然而，人们对cccDNA染色质化与X基因转录之间的关系仍然知之甚少。通过建立一个重组病毒小染色体平台，我们发现cccDNA中的核小体占据驱动了X基因的转录。我们在细胞中证实了这些发现，并进一步表明染色质去稳定分子 CBL137 可抑制肝细胞中的 X 转录和 HBV 感染。我们的研究结果揭示了一个长期存在的悖论，为治疗慢性 HBV 感染提供了一条潜在的新治疗途径。
A nucleosome switch primes Hepatitis B Virus infection.
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.
期刊介绍：
The International Journal of Social Welfare publishes original articles in English on social welfare and social work. Its interdisciplinary approach and comparative perspective promote examination of the most pressing social welfare issues of the day by researchers from the various branches of the applied social sciences. The journal seeks to disseminate knowledge and to encourage debate about these issues and their regional and global implications.
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