Astrocyte activation and dysfunction and neuron death by HIV-1 Tat expression in astrocytes

Betty Y. Zhou, Ying Liu, Byung Oh Kim, Yan Xiao, Johnny J. He

Research output: Contribution to journalArticle

92 Scopus citations

Abstract

Human immunodeficiency virus type 1 (HIV-1) Tat protein plays an important role in HIV-associated neuropathogenesis. Astrocytosis and neuron death are two hallmarks of HIV-1 infection of the central nervous system (CNS). However, whether there is a direct link between Tat expression, astrocytosis and subsequent neuron death is not known. In this study, we expressed Tat in astrocytes and examined Tat effects on astrocyte function and subsequent neuronal survival. The results showed that Tat expression resulted in a significant increase in glial fibrillary acidic protein (GFAP) expression, a cellular marker of astrocyte activation or astrocytosis. The GFAP promoter-driven reporter gene assay showed that Tat transactivated GFAP expression at the transcriptional level. Furthermore, Tat expression markedly impaired glutamate uptake by astrocytes. Importantly, cell culture supernatants from Tat-expressing astrocytes induced dramatic neuron death. Taken together, these data provide evidence for the first time to directly link Tat expression in astrocytes to astrocytosis, astrocyte dysfunction, and subsequent neuron death. In addition, these data suggest that astrocyte dysfunction contributes, at least in part, to Tat neurotoxicity and subsequently HIV-associated neuropathogenesis.

Original languageEnglish
Pages (from-to)296-305
Number of pages10
JournalMolecular and Cellular Neuroscience
Volume27
Issue number3
DOIs
StatePublished - 1 Nov 2004

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