Anatomical, subset, and HIV-dependent expression of viral sensors and restriction factors.

IF 7.5 1区 生物学 Q1 CELL BIOLOGY
Cell reports Pub Date : 2025-01-28 Epub Date: 2025-01-10 DOI:10.1016/j.celrep.2024.115202
Ashley F George, Jason Neidleman, Xiaoyu Luo, Julie Frouard, Natalie Elphick, Kailin Yin, Kyrlia C Young, Tongcui Ma, Alicer K Andrew, Ifeanyi J Ezeonwumelu, Jesper G Pedersen, Antoine Chaillon, Magali Porrachia, Brendon Woodworth, Martin R Jakobsen, Reuben Thomas, Davey M Smith, Sara Gianella, Nadia R Roan
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引用次数: 0

Abstract

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.

病毒传感器和限制因子的解剖、亚群和hiv依赖性表达。
我们开发了病毒传感器和飞行时间限制因子细胞术(VISOR-CyTOF),该技术同时分析了单个细胞中的19个病毒传感器和限制因子(VISORs),并将其应用于41个HIV感染者的死后组织。粘膜髓细胞具有SAMHD1和病毒衣壳和DNA的传感器,而CD4+ T细胞则没有。在淋巴结CD4+ Tfh中,VISOR表达模式反映了有利于整合但阻断HIV基因表达的模式,从而有利于病毒潜伏期。我们还发现了一小部分骨髓、肺和肠道相关CD4+ T细胞和骨髓细胞表达高水平的限制因子,靶向HIV复制周期的大多数阶段。在体外,HIV优先融合到具有允许的VISOR的CD4+ T细胞,但T1IFN早期诱导选择的VISORs可防止HIV感染。我们的研究结果记录了组织和细胞亚群中VISOR谱的不同模式,并定义了它们与HIV易感性的关联。
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来源期刊
Cell reports
Cell reports CELL BIOLOGY-
CiteScore
13.80
自引率
1.10%
发文量
1305
审稿时长
77 days
期刊介绍: Cell Reports publishes high-quality research across the life sciences and focuses on new biological insight as its primary criterion for publication. The journal offers three primary article types: Reports, which are shorter single-point articles, research articles, which are longer and provide deeper mechanistic insights, and resources, which highlight significant technical advances or major informational datasets that contribute to biological advances. Reviews covering recent literature in emerging and active fields are also accepted. The Cell Reports Portfolio includes gold open-access journals that cover life, medical, and physical sciences, and its mission is to make cutting-edge research and methodologies available to a wide readership. The journal's professional in-house editors work closely with authors, reviewers, and the scientific advisory board, which consists of current and future leaders in their respective fields. The advisory board guides the scope, content, and quality of the journal, but editorial decisions are independently made by the in-house scientific editors of Cell Reports.
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