HIV Tat Impairs Neurogenesis through Functioning As a Notch Ligand and Activation of Notch Signaling Pathway.

Abstract

HIV infection of the CNS causes cognitive and memory deficits, which have become more prevalent in the era of combination antiretroviral therapy (cART). Neurogenesis is impaired in HIV-infected individuals. But the underlying molecular mechanisms remain largely unknown. In this study, we have discovered that HIV Tat impairs neurogenesis through the Notch signaling pathway. These findings are particularly important because Tat protein has recently been detected in the brain of HIV-infected individuals with HIV replication in the periphery being effectively controlled by cART. The current study not only further highlights the importance of HIV Tat protein in HIV/neuroAIDS, but also presents a new strategy to develop novel HIV/neuroAIDS therapeutics, particularly in the era of cART.