Characterization of early transcriptomic changes associated with hepatitis B virus exposure in human and macaque immune cell populations. Characterization of early transcriptomic changes associated with hepatitis B virus exposure in human and macaque immune cell populations

Chronic hepatitis B virus (HBV) infection affects close to 300 million individuals worldwide, representing one of the major etiological factors for the development of cirrhosis and hepatocellular carcinoma (HCC). At the molecular level, the mechanisms behind chronic HBV infection are based on the persistence of the viral genome as an episomal structure termed covalently closed circular DNA (cccDNA), and the evasion of both innate and adaptive immune responses. Thus, it is considered that HBV cure will be a multi-layered combination approach of anti-viral and immune-boosting strategies. Although the development of potential HBV therapeutics has been hampered by the lack of suitable long-term infection models, the stark contrast between human and non-human primates regarding their immune responses and infection outcomes, represents an opportunity to identify the molecular mechanisms favoring HBV elimination. Therefore, we aimed to characterize the early transcriptomic changes associated with HBV exposure in human and macaque immune cell populations. Overall design: RNA-Seq profiles from T cells, B cells, myeloid dendritic cells (mDCs) and plasmacytoid dendritic cells (pDCs) with our without HBV exposure (2 h). Experiments were performed for both human and macaque immune cell populations.

慢性乙型肝炎病毒（HBV）感染波及全球近3亿人群，是肝硬化与肝细胞癌（HCC）的主要致病因素之一。在分子层面，慢性HBV感染的发病机制基于病毒基因组以共价闭合环状DNA（cccDNA）这一附加体结构持续存在，以及逃逸先天与适应性免疫应答。因此，学界普遍认为HBV治愈需采用抗病毒与免疫增强策略相结合的多层治疗方案。尽管合适的长期感染模型的匮乏阻碍了潜在HBV治疗药物的研发，但人类与非人灵长类在免疫应答及感染结局上的显著差异，为识别促进HBV清除的分子机制提供了宝贵契机。本研究旨在表征人类与猕猴免疫细胞群体中与HBV暴露相关的早期转录组变化。总体实验设计：对经HBV暴露（2小时）或未暴露的T细胞、B细胞、髓系树突状细胞（mDCs）及浆细胞样树突状细胞（pDCs）开展RNA-Seq表达谱分析，实验覆盖人类与猕猴的两类免疫细胞群体。