Table_4_Delineation and Modulation of the Natural Killer Cell Transcriptome in Rhesus Macaques During ZIKV and SIV Infections.XLSX

Natural killer (NK) cells are crucial regulators of antiviral and anti-tumor immune responses. Although in humans some NK cell transcriptional programs are relatively well-established, NK cell transcriptional networks in non-human primates (NHP) remain poorly delineated. Here we performed RNA-Seq experiments using purified NK cells from experimentally naïve rhesus macaques, providing the first transcriptional characterization of pure NK cells in any NHP species. This novel NK cell transcriptomic signature (NK RMtsig) overlaps with published human NK signatures, allowing us to identify new key signaling and transcription factor networks underlying NK cell function. Finally, we show that applying NK RMtsig to an unrelated rhesus macaque cohort infected with SIVmac251 or ZIKV can sensitively detect NK cell repertoire perturbations, thus confirming applicability of this approach. In sum, we propose this NHP NK cell signature will serve as a useful resource for future studies involving infection, disease or treatment modalities in NHP.

自然杀伤（natural killer，NK）细胞是抗病毒与抗肿瘤免疫应答的关键调控因子。尽管在人类中，部分NK细胞的转录程序已得到较为充分的阐释，但非人灵长类（non-human primates，NHP）体内的NK细胞转录网络仍未得到清晰界定。本研究利用未经历过相关实验处理的恒河猴纯化NK细胞开展RNA测序（RNA-Seq）实验，首次完成了任意非人灵长类物种中纯净NK细胞的转录组特征解析。本研究构建的新型NK细胞转录组特征标记（NK RMtsig）与已发表的人类NK细胞特征标记存在重叠，借此我们得以挖掘调控NK细胞功能的全新关键信号通路与转录因子网络。最后，本研究证实，将NK RMtsig应用于感染猴免疫缺陷病毒mac251株（Simian Immunodeficiency Virus mac251，SIVmac251）或寨卡病毒（Zika virus，ZIKV）的无关恒河猴队列时，可灵敏检测到NK细胞库的扰动，从而验证了该方法的适用性。综上，本研究提出的非人灵长类NK细胞特征标记可作为未来开展非人灵长类感染、疾病或治疗相关研究的宝贵资源。