Evidence for neurotoxic activity of tat from human immunodeficiency virus type 1

Sabatier, Jean‐Marc; Vivès, Éric; Mabrouk, Kamel; Benjouad, Abdelaziz; Rochat, Hervé; Duval, A.; Hue, Bernard; Bahraoui, Elmostafa

doi:10.1128/jvi.65.2.961-967.1991

Cited by 293 publications

(72 citation statements)

References 36 publications

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“…Tat has been detected in the brains and CSF of individuals with NeuroAIDS (Ensoli et al . 1990, 1993) and tat has been shown to be toxic to cultured neurons (Sabatier et al . 1991; Ensoli et al .…”

Section: Discussionmentioning

confidence: 99%

MCP‐1 (CCL2) protects human neurons and astrocytes from NMDA or HIV‐tat‐induced apoptosis

Eugenín¹,

D’Aversa²,

Lopez³

et al. 2003

Journal of Neurochemistry

262

223

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Acquired immunodeficiency syndrome (AIDS)-associated dementia is often characterized by chronic inflammation, with infected macrophage infiltration of the CNS resulting in the production of human immunodeficiency virus type 1 (HIV-1) products, including tat, and neurotoxins that contribute to neuronal loss. In addition to their established role in leukocyte recruitment and activation, we identified an additional role for chemokines in the CNS. Monocyte chemoattractant protein-1 (MCP-1 or CCL2) and regulated upon activation normal T cell expressed and secreted (RANTES) were found to protect mixed cultures of human neurons and astrocytes from tat or NMDA-induced apoptosis. Neuronal and astrocytic apoptosis in these cultures was significantly inhibited by co-treatment with MCP-1 or RANTES but not IP-10. The protective effect of RANTES was blocked by antibodies to MCP-1, indicating that RANTES protection is mediated by the induction of MCP-1. The NMDA blocker, MK801, also abolished the toxic effects of both tat and NMDA. Tat or NMDA treatment of mixed cultures for 24 h resulted in increased extracellular glutamate ([Glu] e ) and NMDA receptor 1 (NMDAR1) expression, potential contributors to apoptosis. Co-treatment with MCP-1 inhibited tat and NMDA-induced increases in [Glu] e and NMDAR1, and also reduced the levels and number of neurons containing intracellular tat. These data indicate that MCP-1 may play a novel role as a protective agent against the toxic effects of glutamate and tat.

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Section: Discussionmentioning

confidence: 99%

MCP‐1 (CCL2) protects human neurons and astrocytes from NMDA or HIV‐tat‐induced apoptosis

Eugenín¹,

D’Aversa²,

Lopez³

et al. 2003

Journal of Neurochemistry

262

223

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“…Viral toxins are proteins released from infected cells including gp120 (Dreyer et al . 1990), Tat (Sabatier et al . 1991; Haughey et al .…”

Section: Substance Abuse and Hiv‐1 Neuropathogenesismentioning

confidence: 99%

HIV‐1 neuropathogenesis: glial mechanisms revealed through substance abuse

Hauser¹,

El‐Hage²,

Stiene‐Martin³

et al. 2006

Journal of Neurochemistry

107

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Neuronal dysfunction and degeneration are ultimately responsible for the neurocognitive impairment and dementia manifest in neuroAIDS. Despite overt neuronal pathology, HIV-1 does not directly infect neurons; rather, neuronal dysfunction or death is largely an indirect consequence of disrupted glial function and the cellular and viral toxins released by infected glia. A role for glia in HIV-1 neuropathogenesis is revealed in experimental and clinical studies examining substance abuse-HIV-1 interactions. Current evidence suggests that glia are direct targets of substance abuse and that glia contribute markedly to the accelerated neurodegeneration seen with substance abuse in HIV-1 infected individuals. Moreover, maladaptive neuroplastic responses to chronic drug abuse might create a latent susceptibility to CNS disorders such as HIV-1. In this review, we consider astroglial and microglial interactions and dysfunction in the pathogenesis of HIV-1 infection and examine how drug actions in glia contribute to neuroAIDS.

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“…Tat is present in the serum and the brain of HIV-infected individuals (Bratanich et al, 1998;Cupp et al, 1993;Kolson et al, 1993;Parmentier et al, 1992;Westendorp et al, 1995a;Xiao et al, 2000b). It causes direct neurotoxicity by various mechanisms including neuroexcitation, Ca 2+ flux, and oxidative stress (Chen et al, 1997;Cheng et al, 1998;Conant et al, 1998;Hofman et al, 1999;Hofman et al, 1994;Hofman et al, 1993;Jones et al, 1998;Liu et al, 2000a;Sabatier et al, 1991;Westendorp et al, 1995b;Zidovetzki et al, 1998;Zocchi et al, 1998). It can also affect neuronal proliferation and differentiation through interaction with cell cycle-related proteins (Milani et al, 1993;Zhou and He, 2004a;Zhou et al, 2004).…”

Section: Introductionmentioning

confidence: 99%

Activation of Egr-1 Expression in Astrocytes by HIV-1 Tat: New Insights into Astrocyte-Mediated Tat Neurotoxicity

Fan

Zou

Green

et al. 2010

J Neuroimmune Pharmacol

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Human immunodeficiency virus type 1 (HIV-1) Tat plays an important role in HIV-associated neuropathogenesis; the underlying mechanisms are still evolving. We have recently shown that HIV-1 Tat induces expression of glial fibrillary acidic protein (GFAP), a characteristic of HIV-1 infection of the central nervous system (CNS). We have also shown that the Tat-induced GFAP expression in astrocytes is regulated by p300, and that deletion of the early growth response 1 (Egr-1) cis-transacting element within the p300 promoter abolishes Tat-induced GFAP expression. In this study, we further examined the relationship between Tat and Egr-1 in astrocytes. We found increased Egr-1 protein expression in Tat-expressing human astrocytoma cells and mouse primary astrocytes. Using the Egr-1 promoter-driven firefly luciferase reporter gene assay and the sitedirected mutagenesis, we demonstrated that Tat increased Egr-1 expression by transactivating the Egr-1 promoter and involving specific serum response elements (SRE) within the promoter. Consistent with these data, we showed that Tat transactivation of the Egr-1 promoter was abrogated when astrocytes were cultured in serum-reduced media. Taken together, these results reveal that Tat directly transactivates Egr-1 expression and suggest that Tat interaction with Egr-1 is probably one of the very upstream molecular events that initiate Tat-induced astrocyte dysfunction and subsequent Tat neurotoxicity.

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Evidence for neurotoxic activity of tat from human immunodeficiency virus type 1

Cited by 293 publications

References 36 publications

MCP‐1 (CCL2) protects human neurons and astrocytes from NMDA or HIV‐tat‐induced apoptosis

MCP‐1 (CCL2) protects human neurons and astrocytes from NMDA or HIV‐tat‐induced apoptosis

HIV‐1 neuropathogenesis: glial mechanisms revealed through substance abuse

Activation of Egr-1 Expression in Astrocytes by HIV-1 Tat: New Insights into Astrocyte-Mediated Tat Neurotoxicity

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