HIV-1 and Amyloid Beta Remodel Proteome of Brain Endothelial Extracellular Vesicles.

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.