Department of Immunology, University of Manitoba, Winnipeg, MB, Canada.
Department of Microbiology, Infectiology and Immunology, Centre de recherche du CHUM and Université de Montréal, Montreal, QC, Canada.
Cell Rep. 2022 Feb 22;38(8):110406. doi: 10.1016/j.celrep.2022.110406.
T cells actively migrate along reticular networks within lymphoid organs in search for cognate antigen, but how these behaviors impact HIV entry and infection is unclear. Here, we show that migratory T cells in 3D collagen matrix display significantly enhanced infection and integration by cell-free R5-tropic lab adapted and transmitted/founder molecular HIV clones in the absence of exogenous cytokines or cationic polymers. Using two different collagen matrices that either support or restrict T cell migration, we observe high levels of HIV fusion in migratory T cells, whereas non-motile T cells display low viral entry and integration. Motile T cells were less sensitive to combination antiretroviral drugs and were able to freely migrate into regions with high HIV densities, resulting in high infection rates. Together, our studies indicate that the environmental context in which initial HIV-T cell encounters occur modulates HIV-1 entry and integration efficiencies.
T 细胞在淋巴器官的网状网络中主动迁移，以寻找同源抗原，但这些行为如何影响 HIV 的进入和感染尚不清楚。在这里，我们表明，在不存在外源性细胞因子或阳离子聚合物的情况下，三维胶原基质中的迁移 T 细胞显著增强了无细胞 R5 嗜性实验室适应和传播/起始分子 HIV 克隆的感染和整合。使用两种不同的胶原基质，一种支持或限制 T 细胞迁移，我们观察到迁移 T 细胞中 HIV 融合的高水平，而非运动 T 细胞显示低病毒进入和整合。运动 T 细胞对联合抗逆转录病毒药物的敏感性较低，并且能够自由迁移到 HIV 密度高的区域，导致高感染率。总之，我们的研究表明，初始 HIV-T 细胞接触发生的环境背景调节了 HIV-1 的进入和整合效率。
