Muratori Claudia, Cavallin Lucas E, Krätzel Kirsten, Tinari Antonella, De Milito Angelo, Fais Stefano, D'Aloja Paola, Federico Maurizio, Vullo Vincenzo, Fomina Alla, Mesri Enrique A, Superti Fabiana, Baur Andreas S
Department of Microbiology and Immunology, University of Miami, Miller School of Medicine, Miami, FL 33136, USA.
Cell Host Microbe. 2009 Sep 17;6(3):218-30. doi: 10.1016/j.chom.2009.06.009.
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 microvesicle 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.
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。在此，我们报告Nef介导的膜转运激活是双向的，将内吞作用与激活的T细胞中发生的胞吐作用联系起来。Nef表达在受感染的T细胞中，令人惊讶的是，在未受感染的T细胞中也诱导了广泛的分泌活性，导致微泡簇的大量释放，这是在体外以及在36%-87%的来自HIV感染者的原代CD4 T细胞中观察到的一种表型。与未感染细胞中的胞吐作用一致，Nef在细胞间接触时转移到旁观者细胞，随后以Erk1/2依赖的方式诱导分泌。因此，HIV Nef改变膜动力学，模仿激活的T细胞的膜动力学，并导致感染细胞信号（TOS）转移到旁观者细胞。这种机制可能有助于解释在HIV感染中观察到的对旁观者细胞的有害影响。
