Investigating the mechanisms involved in HIV infection and cerebral endothelial dysfunction in a 3D human brain neurovascular spheroid.

Nowadays HIV patients are no longer dying from advanced disease but instead, live longer due to effective treatment. However, owing to reasons yet to be fully explained, we see more patients suffering from neurological complications such as stroke and cognitive impairment, that have brain blood vessel dysfunction at their origin. The blood vessel wall is composed of endothelium. This layer of cells closely interacts with other surrounding cells to form a functional unit that controls brain vascular function. It creates a barrier against HIV. Therefore, for HIV to cause vascular complications in the brain, it needs to penetrate this barrier and dysregulate the endothelium. We will assemble a 3D system that mimics the brain environment, and test how HIV penetrates this barrier, establishes infection and causes dysfunction of the endothelium. This study will give insight into the mechanism of vascular disease in the brain and identify potential targets for treatment.