美国威尔康奈尔医学院Yael David小组在研究中取得进展。他们研究出核小体开关引发乙型肝炎病毒感染。相关论文于2025年2月20日发表在《细胞》杂志上。

通过构建重组病毒小染色体平台，该课题组人员发现核小体在cccDNA中的占用调节X的转录。研究人员原位证实了这些发现，并进一步表明染色质不稳定分子CBL137抑制全长X转录和乙肝病毒在原代人肝细胞中的感染。他们的结果揭示了一个长期存在的悖论，并代表了治疗慢性HBV感染的潜在治疗方法。

据了解，慢性乙型肝炎病毒（HBV）感染是一种无法治愈的病原体，可导致导管性肝病和肝细胞癌。在感染发生过程中，HBV建立了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基因在感染后立即表达，诱导宿主沉默因子Smc5/6复合物的降解。然而，cccDNA染色化与X基因转录之间的关系尚不清楚。

附：英文原文

Title: A nucleosome switch primes hepatitis B virus infection

Author: Nicholas A. Prescott, Tracy Biaco, Andrés Mansisidor, Yaron Bram, Justin Rendleman, Sarah C. Faulkner, Abigail A. Lemmon, Christine Lim, Rachel Tiersky, Eralda Salataj, Liliana Garcia-Martinez, Rodrigo L. Borges, Lluis Morey, Pierre-Jacques Hamard, Richard P. Koche, Viviana I. Risca, Robert E. Schwartz, Yael David

Issue&Volume: 2025-02-20

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.

DOI: 10.1016/j.cell.2025.01.033

Source: https://www.cell.com/cell/abstract/S0092-8674(25)00102-3