Nuffield Department of Medicine, University of Oxford, Oxford OX3 7FZ, UK.
Department of Translational Medicine, Università del Piemonte Orientale, 28100 Novara, Italy.
Viruses. 2022 May 17;14(5):1070. doi: 10.3390/v14051070.
Chronic hepatitis B virus (HBV) infection is a global health problem that presents as a spectrum of liver disease, reflecting an interplay between the virus and the host immune system. HBV genomes exist as episomal covalently closed circular DNA (cccDNA) or chromosomal integrants. The relative contribution of these genomes to the viral transcriptome in chronic hepatitis B (CHB) is not well-understood. We developed a qPCR method to estimate the abundance of HBV cccDNA- and integrant-derived viral transcripts and applied this to a cohort of patients diagnosed with CHB in the HBe antigen negative phase of disease. We noted a variable pattern of HBV transcripts from both DNA templates, with preS1/S2 mRNAs predominating and a significant association between increasing age and the expression of integrant-derived mRNAs, but not with inflammatory status. In contrast, cccDNA-derived transcripts were associated with markers of liver inflammation. Analysis of the inflammatory hepatic transcriptome identified 24 genes significantly associated with cccDNA transcriptional activity. Our study uncovers an immune gene signature that associates with HBV cccDNA transcription and increases our understanding of viral persistence.
慢性乙型肝炎病毒 (HBV) 感染是一个全球性的健康问题，表现为一系列肝脏疾病，反映了病毒和宿主免疫系统之间的相互作用。HBV 基因组以附加体共价闭合环状 DNA (cccDNA) 或染色体整合体的形式存在。在慢性乙型肝炎 (CHB) 中，这些基因组对病毒转录组的相对贡献尚不清楚。我们开发了一种 qPCR 方法来估计 HBV cccDNA 和整合体衍生病毒转录物的丰度，并将其应用于在疾病 HBe 抗原阴性阶段被诊断为 CHB 的患者队列。我们注意到两种 DNA 模板的 HBV 转录物存在不同的模式，前 S1/S2 mRNA 占主导地位，年龄增长与整合体衍生 mRNA 的表达呈显著相关，但与炎症状态无关。相比之下，cccDNA 衍生的转录物与肝炎症标志物相关。对炎症性肝转录组的分析确定了 24 个与 cccDNA 转录活性显著相关的基因。我们的研究揭示了与 HBV cccDNA 转录相关的免疫基因特征，并增加了我们对病毒持续存在的理解。
