DataSheet_1_Interspecies comparison of the early transcriptomic changes associated with hepatitis B virus exposure in human and macaque immune cell populations.docx

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）感染影响着全球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复制方面有效，但HBV的根除尚未实现。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方法。非人灵长类动物因其与人类密切的进化关系而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早期对HBV的免疫反应进行了转录组特征化和跨物种比较。方法我们描述了人类和食蟹猴B细胞、T细胞、髓系和浆细胞样树突状细胞（pDC）在HBV体外暴露2小时后的早期转录组变化。差异表达基因进一步与公开可用的单细胞数据中HBV感染患者的特征进行比较。结果HBV在所有细胞类型中引起了广泛的转录组变化，物种间共同的基因仅占很小比例。特别是，干扰素γ信号在人类pDC中被抑制。在基因水平上，干扰素γ诱导蛋白16（IFI16）在食蟹猴pDC中被上调，而在人类中被下调。此外，慢性HBV感染患者的pDC中IFI16的表达与血清HBsAg水平呈反平行。结论我们对人类和食蟹猴HBV诱导的早期转录组变化的描述，是识别共享和不同宿主反应以及针对HBV的潜在免疫靶点的有用资源。