Astrocyte-endothelial Interactions: Implications for Hiv- Associated Neurocognitive Disorder

HIV-associated neurocognitive disorders (HAND) are estimated to affect almost 60% of HIV infected individuals. HIV-encephalitis (HIVE), the pathological correlate of the most severe form of HAND is often characterized by glial activation, cytokine/chemokine dysregulation, and neuronal damage and loss. However, the severity of HIVE correlates better with glial activation rather than viral load. Using the rhesus macaque model, it has been demonstrated that simian immunodeficiency virus encephalitis (SIVE) correlates with increased expression of the mitogen platelet-derived growth factor-B (PDGF-B) chain in the brain. The data therein demonstrate an up-regulation of PDGF-BB in cells exposed to HIV-1 LAI virus which was abrogated by heat-inactivating the virus. Further studies reveal that HIV-1 Tat up-regulated PDGF-B mRNA chain but changes in PDGFA and PDGF-C chains were not evident. Furthermore, Tat preparations, Tat 1-72, Tat 1-86 and Tat 1101 all up-regulated PDGF-BB. The up-regulation of PDGF-BB by Tat was also validated in human primary astrocytes. In an attempt to ascertain the time course of PDGF-B up-regulation, our results reveal a time dependent increase in RNA and protein PDGF-B levels in rat and human astrocyte cell lines C6B2 and A172 as well as human primary cells. The increase in PDGF-BB was further confirmed in vitro by immunostaining. Cumulatively, these data clearly demonstrate HIV-1 Tat-mediated induction of PDGF-BB in human astrocytes and underscores the role that astrocytes