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Occludin, caveolin‐1, and Alix form a multi‐protein complex and regulate HIV‐1 infection of brain pericytes
The FASEB Journal ( IF 4.8 ) Pub Date : 2020-10-14 , DOI: 10.1096/fj.202001562r
Silvia Torices 1 , Samantha A Roberts 1 , Minseon Park 1 , Arun Malhotra 1 , Michal Toborek 1
Affiliation  

HIV‐1 enters the brain by altering properties of the blood‐brain barrier (BBB). Recent evidence indicates that among cells of the BBB, pericytes are prone to HIV‐1 infection. Occludin (ocln) and caveolin‐1 (cav‐1) are critical determinants of BBB integrity that can regulate barrier properties of the BBB in response to HIV‐1 infection. Additionally, Alix is an early acting endosomal factor involved in HIV‐1 budding from the cells. The aim of the present study was to evaluate the role of cav‐1, ocln, and Alix in HIV‐1 infection of brain pericytes. Our results indicated that cav‐1, ocln, and Alix form a multi‐protein complex in which they cross‐regulate each other's expression. Importantly, the stability of this complex was affected by HIV‐1 infection. Modifications of the complex resulted in diminished HIV‐1 infection and alterations of the cytokine profile produced by brain pericytes. These results identify a novel mechanism involved in HIV‐1 infection contributing to a better understanding of the HIV‐1 pathology and the associated neuroinflammatory responses.

中文翻译:

Occludin、caveolin-1 和 Alix 形成多蛋白复合物并调节脑周细胞的 HIV-1 感染

HIV-1 通过改变血脑屏障 (BBB) 的特性进入大脑。最近的证据表明,在 BBB 的细胞中,周细胞易于感染 HIV-1。Occludin (ocln) 和 caveolin-1 (cav-1) 是 BBB 完整性的关键决定因素,可以调节 BBB 的屏障特性以应对 HIV-1 感染。此外,Alix 是一种早期作用的内体因子,参与 HIV-1 从细胞中出芽。本研究的目的是评估 cav-1、ocln 和 Alix 在脑周细胞 HIV-1 感染中的作用。我们的结果表明,cav-1、ocln 和 Alix 形成了一个多蛋白复合物,它们在其中交叉调节彼此的表达。重要的是,该复合物的稳定性受到 HIV-1 感染的影响。复合物的修饰导致 HIV-1 感染减少和脑周细胞产生的细胞因子谱的改变。这些结果确定了一种涉及 HIV-1 感染的新机制,有助于更好地了解 HIV-1 病理学和相关的神经炎症反应。
更新日期:2020-10-14
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