Massive Secretion by T Cells Is Caused by HIV Nef in Infected Cells and by Nef Transfer to Bystander Cells
Massive Secretion by T Cells Is Caused by HIV Nef in Infected Cells and by Nef Transfer to Bystander Cells
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DOI：
10.1016/j.chom.2009.06.009
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发表时间：
2009-09-17
影响因子：
30.3
通讯作者：
Baur, Andreas S.
中科院分区：
文献类型：
--
作者：
Muratori, Claudia;Cavallin, Lucas E.;Baur, Andreas S.
HIV Nef 蛋白介导与疾病进展相关的表面受体的内吞作用，但这种 Nef 功能与 HIV 发病机制之间的联系尚不清楚。在这里，我们报告 Nef 介导的膜运输激活是双向的，将内吞作用与胞吐作用联系起来，就像激活的 T 细胞中发生的那样。 Nef 表达在感染的 T 细胞中诱导了广泛的分泌活性，令人惊讶的是，在未感染的 T 细胞中也如此，导致微泡簇的大量释放，这是一种在体外以及在 HIV 感染者的 36%-87% 的原代 CD4 T 细胞中观察到的表型。与未感染细胞中的胞吐作用一致，Nef 在细胞与细胞接触时转移到旁观者细胞，随后以 Erk1/2 依赖性方式诱导分泌。因此，HIV Nef 会改变膜动力学，模仿激活的 T 细胞的膜动力学，并导致受感染细胞信号传导 (TOS) 转移到旁观者细胞。这种机制可能有助于解释艾滋病毒感染中对旁观者细胞的有害影响。
The HIV Nef protein mediates endocytosis of surface receptors that correlates with disease progression, but the link between this Nef function and HIV pathogenesis is not clear. Here, we report that Nef-mediated activation of membrane trafficking is bidirectional, connecting endocytosis with exocytosis as occurs in activated T cells. Nef expression induced an extensive secretory activity in infected and, surprisingly, also in noninfected T cells, leading to the massive release of microveside clusters, a phenotype observed in vitro and in 36%-87% of primary CD4 T cells from HIV-infected individuals. Consistent with exocytosis in noninfected cells, Nef is transferred to bystander cells upon cell-to-cell contact and subsequently induces secretion in an Erk1/2-dependent manner. Thus, HIV Nef alters membrane dynamics, mimicking those of activated T cells and causing a transfer of infected cell signaling (TOS) to bystander cells. This mechanism may help explain the detrimental effect on bystander cells seen in HIV infection.