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Endothelial Cells Promote Productive HIV Infection of Resting CD4+ T Cells by an Integrin-Mediated Cell Adhesion-Dependent Mechanism
AIDS Research and Human Retroviruses ( IF 1.5 ) Pub Date : 2022-02-04 , DOI: 10.1089/aid.2021.0034
Catherine M Card 1, 2 , Bernard Abrenica 1 , Lyle R McKinnon 2, 3, 4 , Terry Blake Ball 1, 2, 4 , Ruey-Chyi Su 1, 2
Affiliation  

Resting CD4+ T cells are primary targets of early HIV infection events in vivo, but do not readily support HIV replication in vitro. This barrier to infection can be overcome by exposing resting CD4+ T cells to endothelial cells (ECs). ECs line blood vessels and direct T cell trafficking into inflamed tissues. Cell trafficking pathways have been shown to have overlapping roles in facilitating HIV replication, but their relevance to EC-mediated enhancement of HIV susceptibility in resting CD4+ T cells has not previously been examined. We characterized the phenotype of primary human resting CD4+ T cells that became productively infected with HIV when cocultured with primary human blood and lymphatic ECs. The infected CD4+ T cells were primarily central memory cells enriched for high expression of the integrins LFA-1 and VLA-4. ICAM-1 and VCAM-1, the cognate ligands for LFA-1 and VLA-4, respectively, were expressed by the ECs in the coculture. Blocking LFA-1 and VLA-4 on resting CD4+ T cells inhibited infection by 65.4%–96.9%, indicating that engagement of these integrins facilitates EC-mediated enhancement of productive HIV infection in resting CD4+ T cells. The demonstration that ECs influence cellular HIV susceptibility of resting memory CD4+ T cells through cell trafficking pathways engaged during the transmigration of T cells into tissues highlights the physiological relevance of these findings for HIV acquisition and opportunities for intervention.

中文翻译:

内皮细胞通过整合素介导的细胞粘附依赖性机制促进静息 CD4+ T 细胞的生产性 HIV 感染

静止的 CD4 + T 细胞是体内早期 HIV 感染事件的主要目标,但在体外不易支持 HIV 复制。通过将静止的 CD4 + T 细胞暴露于内皮细胞 (EC)可以克服这种感染障碍。EC 排列血管并指导 T 细胞运输到发炎的组织中。细胞运输途径已被证明在促进 HIV 复制方面具有重叠的作用,但它们与 EC 介导的静息 CD4 + T 细胞中 HIV 易感性增强的相关性以前没有被检查过。我们表征了原发性人类静息 CD4 +的表型当与人原代血液和淋巴 EC 共培养时,T 细胞被 HIV 有效感染。受感染的 CD4 + T 细胞主要是富含整合素 LFA-1 和 VLA-4 高表达的中央记忆细胞。ICAM-1 和 VCAM-1,LFA-1 和 VLA-4 的同源配体,分别由共培养中的 EC 表达。在静息 CD4 + T 细胞上阻断 LFA-1 和 VLA-4 可将感染抑制 65.4%–96.9%,表明这些整合素的参与促进了 EC 介导的静息 CD4 + T 细胞中生产性 HIV 感染的增强。ECs 影响静息记忆 CD4 +细胞 HIV 易感性的证明T 细胞通过在 T 细胞迁移到组织过程中参与的细胞运输途径突出了这些发现与 HIV 感染和干预机会的生理相关性。
更新日期:2022-02-08
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