HIV-1 and Amyloid Beta Remodel Proteome of Brain Endothelial Extracellular Vesicles
HIV-1 and Amyloid Beta Remodel Proteome of Brain Endothelial Extracellular Vesicles
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DOI：
10.3390/ijms21082741
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发表时间：
2020-04-01
影响因子：
5.6
通讯作者：
Toborek, Michal
中科院分区：
文献类型：
--
作者：
Andras, Ibolya E.;Sewell, Brice B.;Toborek, Michal
淀粉样蛋白（A β）沉积在hiv感染的大脑中更为丰富。以内皮细胞为骨干的血脑屏障被认为是a - β稳态的核心参与者，可能有助于a - β在大脑中的积累。暴露于HIV会增加人脑内皮细胞的细胞外囊泡（ev）脱落并改变EV-A β水平。电动汽车携带各种货物分子，包括一组复杂的蛋白质，可以深刻地影响周围神经血管单位细胞的生物学。在当前的研究中，我们试图研究暴露于HIV（单独或与A β一起）如何影响脑内皮细胞的表面和总蛋白质组学景观。通过使用这种无偏见的方法，我们对这些变化获得了前所未有的高分辨率洞察。我们的数据表明，HIV和A β深刻地重塑了脑内皮细胞的蛋白质组，改变了通路网络和蛋白质之间的功能相互作用。这些事件可能导致hiv感染大脑中ev介导的淀粉样蛋白病理，并可能与hiv -1相关的神经认知障碍有关。
Amyloid beta (A beta) depositions are more abundant in HIV-infected brains. The blood-brain barrier, with its backbone created by endothelial cells, is assumed to be a core player in A beta homeostasis and may contribute to A beta accumulation in the brain. Exposure to HIV increases shedding of extracellular vesicles (EVs) from human brain endothelial cells and alters EV-A beta levels. EVs carrying various cargo molecules, including a complex set of proteins, can profoundly affect the biology of surrounding neurovascular unit cells. In the current study, we sought to examine how exposure to HIV, alone or together with A beta, affects the surface and total proteomic landscape of brain endothelial EVs. By using this unbiased approach, we gained an unprecedented, high-resolution insight into these changes. Our data suggest that HIV and A beta profoundly remodel the proteome of brain endothelial EVs, altering the pathway networks and functional interactions among proteins. These events may contribute to the EV-mediated amyloid pathology in the HIV-infected brain and may be relevant to HIV-1-associated neurocognitive disorders.