Nrf2 is involved in inhibiting Tat-induced HIV-1 long terminal repeat transactivation

Zhang, Hongsheng; Li, Hongyan; Zhou, Yue; Wu, Meng-Ran; Zhou, Hong-Sen

doi:10.1016/j.freeradbiomed.2009.04.028

Cited by 51 publications

(49 citation statements)

References 43 publications

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“…This paradox might be resolved by considering the differences in Tat levels in the early and late stages of viral infection [Blazek and Peterlin, 2008]. In our previous study, we have shown: (1), Tat decreased the intracellular glutathione (GSH) levels and increased ROS production [Zhang et al, 2009a]. (2), Inhibition of SIRT1 activity by Tat is considered a critical step of Tat transactivation [Zhang et al, 2009b].…”

Section: Nadmentioning

confidence: 99%

Nicotinamide phosphoribosyltransferase/sirtuin 1 pathway is involved in human immunodeficiency virus type 1 Tat‐mediated long terminal repeat transactivation

Zhang

Weiwei

Wang

et al. 2010

J of Cellular Biochemistry

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Tat is a multifunctional transactivator encoded by human immunodeficiency virus type 1 (HIV-1). Tat transactivating activity is controlled by nicotinamide adenine nucleotide(+) (NAD(+))-dependent deacetylase sirtuin 1 (SIRT1). Nicotinamide phosphoribosyltransferase (Nampt) is a rate-limiting enzyme in the conversion of nicotinamide into NAD(+), which is crucial for SIRT1 activation. Thus, the effect of Nampt on Tat-regulated SIRT activity was studied in Hela-CD4-beta-gal (MAGI) cells. We demonstrated that Tat caused NAD(+) depletion and inhibited Nampt mRNA and protein expression in MAGI cells. Resveratrol reversed Tat-induced NAD(+) depletion and inhibition of Nampt mRNA and protein expression. Further investigation revealed that Tat-induced inhibition of SIRT1 activity was potentiated in Nampt-knockdown by Nampt siRNA compared to treatment with Tat alone. Nampt siRNA potentiated Tat-induced HIV-1 transactivation in MAGI cells. Altogether, these results indicate that Nampt is critical in the regulation of Tat-induced inhibition of SIRT1 activity and long terminal repeat (LTR) transactivation. Nampt/SIRT1 pathway could be a novel therapeutic tool for the treatment of HIV-1 infection.

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Section: Nadmentioning

confidence: 99%

Nicotinamide phosphoribosyltransferase/sirtuin 1 pathway is involved in human immunodeficiency virus type 1 Tat‐mediated long terminal repeat transactivation

Zhang

Weiwei

Wang

et al. 2010

J of Cellular Biochemistry

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“…Other HIV-1 proteins have been found to induce OS (Lassiter et al , 2009). Tat induces ROS accumulation through Nrf2 (Zhang et al , 2009) and inducible nitric oxide synthase signaling in astroglia (Liu et al , 2002), activation of macrophages and microglial cells, as well as T-cell infiltration in the CNS (Zhou et al , 2007), while gp120 sensitizes neurons to hydrogen peroxide-induced OS (Agrawal et al , 2009). HIV-1 viral protein R (Vpr) was found to induce OS through the hypoxia-inducible factor pathway in microglia (Deshmane et al , 2009), and we recently demonstrated Vpr as a causative agent of OS in an astroglioma cell line through depletion of ATP and GSH reservoirs (Ferrucci et al , 2012).…”

Section: Introductionmentioning

confidence: 99%

Extracellular HIV-1 viral protein R affects astrocytic glyceraldehyde 3-phosphate dehydrogenase activity and neuronal survival

2013

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Extracellular human immunodeficiency virus type type 1 (HIV-1) viral protein R (Vpr) is a pleiotropic protein accomplishing several functions within the viral life cycle. While Vpr has been described extensively as an intracellular protein, very little is known about its role as an extracellular protein. In fact, HIV-1 Vpr has been detected in the blood, serum, and cerebrospinal fluid of HIV-1-infected patients, with concentrations increasingly higher in late-stage disease. To determine the role exogenous Vpr plays in HIV-associated central nervous system dysfunction, primary human fetal astrocytes were exposed to recombinant Vpr and a time- and dose-dependent decrease was demonstrated in two fundamental intracellular metabolites (ATP and glutathione (GSH)). Additionally, exposure to exogenous Vpr led to increased caspase activity and secretion of proinflammatory cytokines IL-6 and IL-8 and chemoattractants, monocyte chemotactic protein-1 and migration inhibition factor. Extracellular Vpr also dampened the glycolytic pathway through impairment of GAPDH activity, causing a decline in the levels of ATP. The reduction in intracellular ATP increased reactive oxygen species buildup, decreasing GSH concentrations, which affected several genes in the oxidative stress pathway. In addition, exposure of the SK-N-SH neuroblastoma cell line to conditioned medium from exogenous Vpr-treated astrocytes decreased synthesis of GSH, leading to their apoptosis. These observations point to a role that Vpr plays in altering astrocytic metabolism and indirectly affecting neuronal survival. We propose a model that may explain some of the neurological damage and therefore neurocognitive impairment observed during the course of HIV-1 disease.

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“…74,75 The inhibited activity of both the p38 MAPK and JAK-STAT pathways in B16 ex vivo cells facilitated alphavirus replication and transgene expression, possibly by delaying the onset of apoptosis during infection. The downregulation of several genes coordinated by the IFN-inducible pathways shown in Table S3 such us Nfe2l, [77][78][79] Ifi35, 80 S100A11 81 has been shown to promote different levels of virus infectivity.…”

Section: Role Of Antiviral Response Genes In Viral Activitymentioning

confidence: 99%

Comparative protein profiling of B16 mouse melanoma cells susceptible and non-susceptible to alphavirus infection: Effect of the tumor microenvironment

Vasilevska

Souza

Stensland

et al. 2016

Cancer Biology & Therapy

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Alphavirus vectors are promising tools for cancer treatment. However, relevant entry mechanisms and interactions with host cells are still not clearly understood. The first step toward a more effective therapy is the identification of novel intracellular alterations that could be associated with cancer aggressiveness and could affect the therapeutic potential of these vectors. In this study, we observed that alphaviruses efficiently infected B16 mouse melanoma tumors/tumor cells in vivo, whereas their transduction efficiency in B16 cells under in vitro conditions was blocked. Therefore, we further aimed to understand the mechanisms pertaining to the differential transduction efficacy of alphaviruses in B16 tumor cells under varying growth conditions. We hypothesized that the tumor microenvironment might alter gene expression in B16 cells, leading to an up-regulation of the expression of virus-binding receptors or factors associated with virus entry and replication. To test our hypothesis, we performed a proteomics analysis of B16 cells cultured in vitro and of B16 cells isolated from tumors, and we identified 277 differentially regulated proteins. A further in-depth analysis to identify the biological and molecular functions of the detected proteins revealed a set of candidate genes that could affect virus infectivity. Importantly, we observed a decrease in the expression of interferon a (IFN-a) in tumor-isolated cells that resulted in the suppression of several IFN-regulated genes, thereby abrogating host cell antiviral defense. Additionally, differences in the expression of genes that regulate cytoskeletal organization caused significant alterations in cell membrane elasticity. Taken together, our findings demonstrated favorable intracellular conditions for alphavirus transduction/replication that occurred during tumor transformation. These results pave the way for optimizing the development of strategies for the application of alphaviral vectors as a potent cancer therapy.

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Nrf2 is involved in inhibiting Tat-induced HIV-1 long terminal repeat transactivation

Cited by 51 publications

References 43 publications

Nicotinamide phosphoribosyltransferase/sirtuin 1 pathway is involved in human immunodeficiency virus type 1 Tat‐mediated long terminal repeat transactivation

Nicotinamide phosphoribosyltransferase/sirtuin 1 pathway is involved in human immunodeficiency virus type 1 Tat‐mediated long terminal repeat transactivation

Extracellular HIV-1 viral protein R affects astrocytic glyceraldehyde 3-phosphate dehydrogenase activity and neuronal survival

Comparative protein profiling of B16 mouse melanoma cells susceptible and non-susceptible to alphavirus infection: Effect of the tumor microenvironment

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