Naidu Samrita, Margeridon Severine
Virology, Rio Americano High School, Sacramento, USA.
Molecular Diagnostics and Assay Development, Bio-Rad Laboratories, San Francisco, USA.
Cureus. 2025 Feb 13;17(2):e78944. doi: 10.7759/cureus.78944. eCollection 2025 Feb.
Chronic hepatitis B (CHB) virus infection can lead to severe liver diseases, including cirrhosis and hepatocellular carcinoma. The chronicity of the hepatitis B virus (HBV) occurs because of the persistence of viral covalently closed circular DNA (cccDNA) within hepatocytes. The cccDNA serves as the template for viral replication and is central to HBV, maintaining a viral reservoir within the host. Despite therapeutic advancements, eliminating cccDNA remains elusive due to its evasion of immune surveillance. This review explores the formation and maintenance of cccDNA, highlighting host factors influencing cccDNA stability and viral replication. It also discusses current treatment strategies, including interferon-based therapies and nucleoside/nucleotide analogs, which aim to suppress viral replication. Emerging therapies such as gene editing and molecular interventions hold promise for targeting cccDNA directly. Currently, research is focused on making medications that target host factors of interest to disrupt or clear the viral reservoir. However, future research should focus on innovative approaches that directly target the cccDNA minichromosome, aiming for sustained viral suppression and potentially a cure for the HBV infection.
慢性乙型肝炎（CHB）病毒感染可导致严重的肝脏疾病，包括肝硬化和肝细胞癌。乙型肝炎病毒（HBV）的慢性化是由于病毒共价闭合环状DNA（cccDNA）在肝细胞内持续存在所致。cccDNA作为病毒复制的模板，对HBV至关重要，它在宿主体内维持着一个病毒储存库。尽管治疗取得了进展，但由于cccDNA能逃避免疫监视，消除它仍然难以实现。本综述探讨了cccDNA的形成和维持，强调了影响cccDNA稳定性和病毒复制的宿主因素。它还讨论了当前的治疗策略，包括基于干扰素的疗法和核苷/核苷酸类似物，这些疗法旨在抑制病毒复制。基因编辑和分子干预等新兴疗法有望直接靶向cccDNA。目前，研究集中在开发针对相关宿主因子的药物，以破坏或清除病毒储存库。然而，未来的研究应聚焦于直接靶向cccDNA微型染色体的创新方法，目标是持续抑制病毒并有可能治愈HBV感染。
