HIV Tat 101-mediated loss of pericytes at the blood-brain barrier involves PDGF-BB.

Abstract

HIV-1-associated neurocognitive disorders (HAND) affect almost 30-50% of infected individuals, even in the presence of successful control of virus replication by combined antiretroviral therapy (cART).HIV Tat protein, a nuclear trans-activator of viral gene transcription, that is secreted by infected cells and can be taken up by the neighboring cells, is present in various tissues despite the presence of cART, and has been shown to break down the integrity of the blood-brain barrier (BBB). This, in turn, leads to disruption of the neovascular unit, affecting functioning of the brain microvascular endothelial cells as well as astrocytes. Pericytes, yet another important constituent of the BBB, play a critical role in the maintenance of the integrity of the BBB. Loss of pericytes resulting in disruption of BBB has been observed in several pathologies including HAND. Furthermore, while PDGF-BB is essential for pericyte generation, paradoxically, high concentrations of PDGF-BB lead to loss of pericytes in tumor vessels. In this research highlight, we provide a brief review of our recently published finding, which have demonstrated a novel role of PDGF-BB in HIV-Tat mediated migration of pericytes, leading ultimately to loss of pericyte coverage from the endothelium, with a subsequent breach of the BBB. These findings underpin yet another mechanism by which BBB integrity is disrupted in HAND.