Table_1_Interspecies comparison of the early transcriptomic changes associated with hepatitis B virus exposure in human and macaque immune cell populations.xlsx

Background and aimsHepatitis B virus (HBV) infection affects 300 million individuals worldwide, representing a major factor for the development of hepatic complications. Although existing antivirals are effective in suppressing replication, eradication of HBV is not achieved. Therefore, a multi-faceted approach involving antivirals and immunomodulatory agents is required. Non-human primates are widely used in pre-clinical studies due to their close evolutionary relationship to humans. Nonetheless, it is fundamental to identify the differences in immune response between humans and these models. Thus, we performed a transcriptomic characterization and interspecies comparison of the early immune responses to HBV in human and cynomolgus macaques.MethodsWe characterized early transcriptomic changes in human and cynomolgus B cells, T cells, myeloid and plasmacytoid dendritic cells (pDC) exposed to HBV ex vivo for 2 hours. Differentially-expressed genes were further compared to the profiles of HBV-infected patients using publicly-available single-cell data.ResultsHBV induced a wide variety of transcriptional changes in all cell types, with common genes between species representing only a small proportion. In particular, interferon gamma signaling was repressed in human pDCs. At the gene level, interferon gamma inducible protein 16 (IFI16) was upregulated in macaque pDCs, while downregulated in humans. Moreover, IFI16 expression in pDCs from chronic HBV-infected patients anti-paralleled serum HBsAg levels.ConclusionOur characterization of early transcriptomic changes induced by HBV in humans and cynomolgus macaques represents a useful resource for the identification of shared and divergent host responses, as well as potential immune targets against HBV.

背景与目标乙型肝炎病毒（HBV）感染全球影响3亿人口，是导致肝部并发症的主要因素。尽管现有的抗病毒药物在抑制病毒复制方面有效，但HBV的根除并未实现。因此，需要采用包括抗病毒药物和免疫调节剂在内的多方面策略。由于非人灵长类动物与人类具有密切的进化关系，它们在临床前研究中被广泛使用。然而，识别人类与这些模型之间免疫反应的差异是至关重要的。因此，我们对人类和食蟹猴在HBV早期免疫反应中的转录组进行了特征描述和种间比较。方法我们对暴露于HBV的2小时外的人类和食蟹猴B细胞、T细胞、髓系和浆细胞样树突状细胞（pDC）的早期转录组变化进行了表征。差异表达的基因随后与公开可用的单细胞数据中HBV感染患者的轮廓进行了比较。结果HBV在所有细胞类型中诱导了广泛的转录组变化，物种间共同的基因仅占一小部分。特别是，干扰素γ信号在人类pDCs中被抑制。在基因水平上，干扰素γ诱导蛋白16（IFI16）在食蟹猴pDCs中上调，而在人类中下调。此外，慢性HBV感染患者pDCs中的IFI16表达与血清HBsAg水平呈抗平行关系。结论我们对HBV在人类和食蟹猴中诱导的早期转录组变化的表征，是识别共享和差异宿主反应以及针对HBV的潜在免疫靶点的有用资源。