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Khayalihle Brian Makhathini

University of the Western Cape, South Africa

Presentation Title:

The neurodegenerative effects of HIV-proteins on the blood-brain barrier endothelial cells

Abstract

Human immunodeficiency virus type 1 (HIV-1) remains a global health threat, particularly in South Africa. The virus can enter the central nervous system (CNS) within days of infection, potentially leading to HIV-associated neurocognitive disorder (HAND), which continues to affect many people living with HIV. HIV crosses the blood-brain barrier (BBB) in many ways, some through infected monocytes. The BBB, a crucial barrier protecting the CNS, limits the penetration of many drugs, including highly active antiretroviral therapy (HAART), which effectively reduces HIV in the peripheral system but struggles to reach the CNS. This presents challenges in treating HIV-associated neurocognitive impairments.

This study evaluated the effects of co-culture and paracrine factors from HL2/3 cells (which express and secrete HIV proteins) on an in vitro BBB model. The model was developed by co-culturing HL2/3 cells and selecting the HIV-Protein factors (HIV-PFs) concentration with bEnd-5 brain endothelial cells to simulate the physiological interactions between HIV and the BBB. In the experimental model, we assessed various physiological parameters, including cell proliferation, viability, toxicity, and cell division in monocultures. The physiological integrity of the bEnd5 cell monolayers was assessed by monitoring the monolayer permeability using transendothelial electrical resistance (TEER).

Our results showed that HIV-PFs and HL2/3 cell co-culture conditions decreased endothelial cell proliferation by primarily suppressing bEnd5 cell division and, secondarily, by increasing bEnd5 cell toxicity. In parallel, HIV-PFs increased BBB permeability in a dose-dependent manner.

Recent studies have demonstrated that the brain has become the reservoir for HIV, which leads to the development of HIV-associated neurocognitive disorders (HAND). Therefore, it is essential to understand the HIV pathophysiological mechanism of the primary component of the BBB, the brain capillary endothelium. These findings offer important insights into the mechanisms contributing to HAND and to developing effective therapeutics.

Biography

TBA