单细胞多组学揭示了 HIV-1 在扩增的细胞毒性 T 细胞克隆中的持续存在。
Single-cell multiomics reveals persistence of HIV-1 in expanded cytotoxic T cell clones.
机构信息
Department of Microbial Pathogenesis, Yale University School of Medicine, New Haven, CT 06519, USA.
Vaccine and Infectious Disease, Fred Hutchinson Cancer Research Center, Seattle, WA, 98109, USA.
出版信息
Immunity. 2022 Jun 14;55(6):1013-1031.e7. doi: 10.1016/j.immuni.2022.03.004. Epub 2022 Mar 22.
Understanding the drivers and markers of clonally expanding HIV-1-infected CD4 T cells is essential for HIV-1 eradication. We used single-cell ECCITE-seq, which captures surface protein expression, cellular transcriptome, HIV-1 RNA, and TCR sequences within the same single cell to track clonal expansion dynamics in longitudinally archived samples from six HIV-1-infected individuals (during viremia and after suppressive antiretroviral therapy) and two uninfected individuals, in unstimulated conditions and after CMV and HIV-1 antigen stimulation. Despite antiretroviral therapy, persistent antigen and TNF responses shaped T cell clonal expansion. HIV-1 resided in Th1-polarized, antigen-responding T cells expressing BCL2 and SERPINB9 that may resist cell death. HIV-1 RNA T cell clones were larger in clone size, established during viremia, persistent after viral suppression, and enriched in GZMB cytotoxic effector memory Th1 cells. Targeting HIV-1-infected cytotoxic CD4 T cells and drivers of clonal expansion provides another direction for HIV-1 eradication.
了解驱动和标记克隆扩增的 HIV-1 感染的 CD4 T 细胞对于 HIV-1 的根除至关重要。我们使用单细胞 ECCITE-seq，该技术可以在同一个单细胞中捕获表面蛋白表达、细胞转录组、HIV-1 RNA 和 TCR 序列，以跟踪来自六名 HIV-1 感染者（在病毒血症期间和抑制性抗逆转录病毒治疗后）和两名未感染者的纵向存档样本中的克隆扩增动力学，在未刺激条件下以及在 CMV 和 HIV-1 抗原刺激后。尽管进行了抗逆转录病毒治疗，但持续的抗原和 TNF 反应塑造了 T 细胞的克隆扩增。HIV-1 存在于 Th1 极化的、表达 BCL2 和 SERPINB9 的抗原反应性 T 细胞中，这些细胞可能抵抗细胞死亡。HIV-1 RNA T 细胞克隆在病毒血症期间建立、病毒抑制后持续存在且在 GZMB 细胞毒性效应记忆 Th1 细胞中富集时，其克隆大小更大。针对 HIV-1 感染的细胞毒性 CD4 T 细胞和克隆扩增的驱动因素为 HIV-1 的根除提供了另一个方向。
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