George Ashley F, Neidleman Jason, Luo Xiaoyu, Frouard Julie, Elphick Natalie, Yin Kailin, Young Kyrlia C, Ma Tongcui, Andrew Alicer K, Ezeonwumelu Ifeanyi J, Pedersen Jesper G, Chaillon Antoine, Porrachia Magali, Woodworth Brendon, Jakobsen Martin R, Thomas Reuben, Smith Davey M, Gianella Sara, Roan Nadia R
Gladstone Institutes, San Francisco, CA, USA; Department of Urology, UCSF, San Francisco, CA, USA.
Gladstone Institutes, San Francisco, CA, USA.
Cell Rep. 2025 Jan 28;44(1):115202. doi: 10.1016/j.celrep.2024.115202. Epub 2025 Jan 10.
We developed viral sensor and restriction factor-cytometry by time of flight (VISOR-CyTOF), which profiles 19 viral sensors and restriction factors (VISORs) simultaneously in single cells, and applied it to 41 postmortem tissues from people with HIV. Mucosal myeloid cells are well equipped with SAMHD1 and sensors of viral capsid and DNA while CD4 T cells are not. In lymph node CD4 Tfh, VISOR expression patterns reflect those favoring integration but blocking HIV gene expression, thus favoring viral latency. We also identify small subsets of bone marrow-, lung-, and gut-associated CD4 T and myeloid cells expressing high levels of restriction factors targeting most stages of the HIV replication cycle. In vitro, HIV preferentially fuses to CD4 T cells with a permissive VISOR profile, but early induction of select VISORs by T1IFN prevents productive HIV infection. Our findings document the diverse patterns of VISOR profiles across tissues and cellular subsets and define their association with susceptibility to HIV.
我们开发了飞行时间病毒传感器和限制因子细胞计数法（VISOR-CyTOF），该方法可在单细胞中同时分析19种病毒传感器和限制因子（VISOR），并将其应用于41例HIV感染者的尸检组织。黏膜髓样细胞配备有SAMHD1以及病毒衣壳和DNA传感器，而CD4 T细胞则没有。在淋巴结CD4 Tfh中，VISOR表达模式反映出有利于整合但阻断HIV基因表达的模式，从而有利于病毒潜伏。我们还鉴定出骨髓、肺和肠道相关的CD4 T细胞和髓样细胞的小亚群，它们表达针对HIV复制周期大多数阶段的高水平限制因子。在体外，HIV优先与具有允许性VISOR谱的CD4 T细胞融合，但T1IFN对选定VISOR的早期诱导可防止HIV的有效感染。我们的研究结果记录了不同组织和细胞亚群中VISOR谱的多样模式，并确定了它们与HIV易感性的关联。
