Pilot Award Recipient: Kyle A. DiVito

A number of neurological disorders have been observed in people living with HIV (PWH), even while receiving antiretroviral therapies. These so-called HAND disorders (HIV-Associated Neurological Disorders) are characterized by muscle tremors, reduced coordination and eventually loss of fine motor skills. These comorbidities can be significantly debilitating to PWH, and the impact on their families should not go over-looked. Our current understanding of HAND is limited, yet data suggests that chronic inflammation pays a significant role. However, exactly how chronic inflammation results in HAND is not yet known. This work will assess how supporting cell types in the brain, known as astrocytes, can uptake the Nef-1 viral protein, transmit viral protein into neighboring lymphatic vessels and thus trigger the immunosecretome. We hypothesize that viral proteins released from astrocytes can lead to lymphatic endothelial dysfunction and take advantage of the lymphatic drainage system present in the brain. We will explore inflammatory biomarkers including CXCR4, Il-6, Il-8 and TNF-alpha in lymphatic endothelial cells in response to Nef-1. Using microfluidics and 3D bioprinting, this proposal will develop a novel lymphatic system to recreate this organ system. This proposal will assess each cell-type of the organ system, learn how HIV-derived viral proteins from latency can over-activate the immune system and eventually contribute to HAND disorders in a biomimetic system that better models human disease in PWH.

Project Summary provided by investigator.