Integrin α4β7 Expression Increases HIV Susceptibility in Activated Cervical CD4+ T Cells by an HIV Attachment-Independent Mechanism.
Integrin α4β7 Expression Increases HIV Susceptibility in Activated Cervical CD4+ T Cells by an HIV Attachment-Independent Mechanism.
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DOI：
10.1097/qai.0000000000000676
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发表时间：
2015-08-15
期刊：
影响因子：
--
通讯作者：
Chang TL
中科院分区：
文献类型：
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作者：
Ding J;Tasker C;Lespinasse P;Dai J;Fitzgerald-Bocarsly P;Lu W;Heller D;Chang TL
CD4+T细胞是急性SIV和HIV感染的主要靶点，对粘膜组织中HIV感染的建立和传播至关重要。研究表明，在体外和急性α感染过程中，β_4、CD_4、CD_4~+T细胞优先感染HIV。整合素α4β7被认为可以促进靶细胞捕获艾滋病毒；然而，整合素α4β7在艾滋病毒传播中的作用仍然存在争议。在这项研究中，我们确定了人宫颈T细胞的免疫表型，并检测了整合素α4 CD4+β+T细胞对HIV的偏好。以全反式维甲酸分化的外周血中的CD4+T细胞(at-RA分化细胞)作为对照。在感染的AT-RA分化细胞中，HIVp24+细胞表达α4β7的频率高于HIVp24-细胞，而在宫颈细胞中无明显差异。环状六肽CWLDVC和抗整合素α4β7的单抗都不能阻止α4β7与靶细胞的结合或结合，表明整合素CD4 GP7不能促进靶细胞捕获HIV。整合素α4β7的表达增加了艾滋病毒的易感性，但其机制并不是通过促进艾滋病毒与靶细胞的结合来实现的。
CD4+ T cells, the principal target in acute SIV and HIV infection, are crucial for the establishment and dissemination of HIV infection in mucosal tissues. Studies indicate that α4β7 CD4+ T cells are preferentially infected by HIV in vitro and during acute SIV infection. The integrin α4β7 is thought to promote HIV capture by target cells; however, the role of integrin α4β7 in HIV transmission remains controversial. In this study, we characterized immune phenotypes of human cervical T cells and examined HIV preference in integrin α4β7+ CD4+ T cells. In vitro all-trans retinoic acid differentiated peripheral CD4+ T cells (at-RA differentiated cells) were included as a comparison. In both peripheral and cervical cells, the majority of HIV p24+ cells were activated CD4+ T cells expressing integrin α4β7. Among infected at-RA differentiated cells, the frequency of CCR5 expression was higher in HIV p24+ cells than in HIV p24- cells; no such difference was observed in cervical cells. Neither the cyclic hexapeptide CWLDVC nor a monoclonal antibody against integrin α4β7 blocked HIV attachment or gp120 binding to target cells regardless of the presence of CD4, indicating that integrin α4β7 did not facilitate HIV capture by target cells. Integrin α4β7 expression increases HIV susceptibility, but the mechanism is not through promoting HIV binding to target cells.