Extracellular vesicles of the blood-brain barrier: Role in the HIV-1 associated amyloid beta pathology.

ABSTRACT: HIV-infected brains are characterized by increased amyloid beta (A?) deposition. It is believed that the blood-brain barrier (BBB) is critical for A? homeostasis and contributes to A? accumulation in the brain. Extracellular vesicles (ECV), like exosomes, recently gained a lot of attention as potentially playing a significant role in A? pathology. In addition, HIV-1 hijacks the exosomal pathway for budding and release. Therefore, we investigated the involvement of BBB-derived ECV in the HIV-1-induced A? pathology in the brain. Our results indicate that HIV-1 increases ECV release from brain endothelial cells as well as elevates their A? cargo when compared to controls. Interestingly, brain endothelial cell-derived ECV transferred A? to astrocytes and pericytes. Infusion of brain endothelial ECV carrying fluorescent A? into the internal carotid artery of mice resulted in A? fluorescence associated with brain microvessels and in the brain parenchyma. These results suggest that ECV carrying A? can be successfully transferred across the BBB into the brain. Based on these observations, we conclude that HIV-1 facilitates the shedding of brain endothelial ECV carrying A?; a process that may increase A? exposure of cells of neurovascular unit, and contribute to amyloid deposition in HIV-infected brain.

SUBMITTER: Andras IE 

PROVIDER: S-EPMC5315639 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature