Th17 T Cells and Immature Dendritic Cells Are the Preferential Initial Targets after Rectal Challenge with a Simian Immunodeficiency Virus-Based Replication-Defective Dual-Reporter Vector
Th17 T Cells and Immature Dendritic Cells Are the Preferential Initial Targets after Rectal Challenge with a Simian Immunodeficiency Virus-Based Replication-Defective Dual-Reporter Vector
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DOI：
10.1128/jvi.00707-21
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发表时间：
2021-10-01
影响因子：
5.4
通讯作者：
Hope, Thomas J.
中科院分区：
文献类型：
--
作者：
Maric, Danijela;Grimm, Wesley A.;Hope, Thomas J.
了解人类免疫缺陷病毒（HIV）性传播的早期事件对于制定和优化HIV预防战略至关重要。为了深入了解HIV直肠传播的最早步骤，包括细胞靶点，恒河猴直肠内用单轮猴免疫缺陷病毒（SIV）为基础的双报告基因进行了攻击，该双报告基因在生产性转导后表达荧光素酶和近红外荧光蛋白670（iRFP 670）。用HIV-1包膜JRFL对载体进行假型化。使用体内成像系统在宏观上鉴定含有发光转导细胞灶的组织区域，并在显微镜下鉴定表达荧光蛋白的单个转导细胞并进行表型分析。该系统揭示了肛门和直肠组织在直肠激发后48小时都对转导敏感。详细的表型分析显示，平均62%的转导细胞是CCR 6阳性（CCR 61）T细胞，其中绝大多数表达RORgT，一种Th 17谱系特异性转录因子。第二常见的靶细胞是未成熟树突状细胞，占20%。这两种细胞类型以比它们的相对丰度指示高四到五倍的速率转导。我们的工作表明，Th 17 T细胞和未成熟的树突状细胞是HIV/SIV直肠transmittance.IMPORTANCE男性和女性谁参加无保护的接受肛交是在获得艾滋病毒的高风险的优先初始目标。虽然体外数据已经为理解HIV细胞嗜性建立了一个框架，但直肠粘膜中的初始靶细胞尚未确定。在这项研究中，我们通过使用我们以前开发的创新恒河猴直肠挑战模型和方法来识别这些早期宿主细胞。因此，通过揭示这些早期HIV/SIV传播事件，这项研究为未来的预防策略提供了一个特定的细胞靶点。
Understanding the earliest events of human immunodeficiency virus (HIV) sexual transmission is critical to developing and optimizing HIV prevention strategies. To gain insights into the earliest steps of HIV rectal transmission, including cellular targets, rhesus macaques were intrarectally challenged with a single-round simian immunodeficiency virus (SIV)-based dual reporter that expresses luciferase and near infrared fluorescent protein 670 (iRFP670) upon productive transduction. The vector was pseudotyped with the HIV-1 envelope JRFL. Regions of tissue containing foci of luminescent transduced cells were identified macroscopically using an in vivo imaging system, and individual transduced cells expressing fluorescent protein were identified and phenotyped microscopically. This system revealed that anal and rectal tissues are both susceptible to transduction 48 h after the rectal challenge. Detailed phenotypic analysis revealed that, on average, 62% of transduced cells are CCR6-positive (CCR61) T cells-the vast majority of which express RORgT, a Th17 lineage-specific transcription factor. The second most common target cells were immature dendritic cells at 20%. These two cell types were transduced at rates that are four to five times higher than their relative abundances indicate. Our work demonstrates that Th17 T and immature dendritic cells are preferential initial targets of HIV/SIV rectal transmission.IMPORTANCE Men and women who participate in unprotected receptive anal intercourse are at high risk of acquiring HIV. While in vitro data have developed a framework for understanding HIV cell tropism, the initial target cells in the rectal mucosa have not been identified. In this study, we identify these early host cells by using an innovative rhesus macaque rectal challenge model and methodology, which we previously developed. Thus, by shedding light on these early HIV/SIV transmission events, this study provides a specific cellular target for future prevention strategies.