Resveratrol inhibited Tat-induced HIV-1 LTR transactivation via NAD+-dependent SIRT1 activity

Zhang, Hongsheng; Zhou, Yue; Wu, Meng-Ran; Zhou, Hong-Sen; Xu, Fei

doi:10.1016/j.lfs.2009.07.014

Cited by 51 publications

(43 citation statements)

References 35 publications

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“…Starting from the reports available in literature in which SIRT1 and its positive modulation by resveratrol inhibit varicella zoster virus replication, [24], human immunodeficiency virus type 1 (HIV-1) long terminal repeat (LTR) [25] transactivation, and viral transgene expression of adenovirus in neuronal cells [26], Shenk et al [27] patented the effects of the known sirtuin inhibitors EX-527, cambinol, tenovin-6, salermide, and of the SIRT1 activators resveratrol and the pyrroloquinoxaline CAY10602 ( Figure 1) in virus production. First, the authors demonstrated that the prominent positive effect on human cytomegalovirus (HCMV) replication in infected MRC5 fibroblasts was mainly observed when mitochondrial SIRT3--5 were inhibited by short interfering RNA (siRNA), thus indicating for the first time that the activation of those isoforms could be useful targets for antiviral therapy.…”

Section: Sirtuin Inhibitorsmentioning

confidence: 99%

Sirtuin modulators: an updated patent review (2012 – 2014)

Mellini

Valente

Mai

2014

Expert Opinion on Therapeutic Patents

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The effective role of sirtuins in cancer is still controversial, because some of them seem to have tumor-promoter as well as tumor-suppressor properties. Thus, few patents describing SIRT inhibitors have been found in 2012 - 2014 period. Despite the still active debate on their role as direct or indirect activators of SIRT1, sirtuin-activating compounds are actually subjected to intense research for the ability to treat neurodegenerative diseases, metabolic disorders, inflammation, vascular system injuries, wound healing and endothelial dysfunctions. A great number of clinical trials are reported with either SIRT inhibitors or activators, thus it is possible that in the foreseeable future one or more of them will enter in the clinical arena.

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Section: Sirtuin Inhibitorsmentioning

confidence: 99%

Sirtuin modulators: an updated patent review (2012 – 2014)

Mellini

Valente

Mai

2014

Expert Opinion on Therapeutic Patents

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“…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]. (3), The NAD þ -SIRT1-AMPK signaling pathway may be activated by reduced nutrient availability to prevent Tat-induced HIV-1 LTR transactivation [Zhang and Wu, 2009].…”

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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“…Additionally, pretreatment of resveratrol, an SIRT1 inhibitor, attenuated Tat-mediated HIV-1 transactivation through modulating the redox status of the cell. 110 Although its precise mechanism of action is yet to be identified, the 1-8-naphthyridone derivative (HM13N) has been shown to inhibit HIV-1 Tat-mediated transcription. It displayed very potent and selective anti-HIV activity in acutely (EC 50 0.0.2-0.3 lg/ml), chronically (EC 50 0.032 lg/ml), and latently infected cells (0.003-0.004 lg/ml).…”

Section: Tatmentioning

confidence: 99%

Transcriptional Control of HIV Replication by Multiple Modulators and Their Implication for a Novel Antiviral Therapy

Victoriano

Okamoto

2012

AIDS Research and Human Retroviruses

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Transcriptional regulation is critical for the human immunodeficiency virus 1 (HIV-1) life cycle and is the only step at which the virus amplifies the content of its genetic information. Numerous known and still unknown transcriptional factors, both host and viral, regulate HIV-1 gene expression and latency. This article is a comprehensive review of transcription factors involved in HIV-1 gene expression and presents the significant implications of nuclear factor kappa B (NF-κB) and the HIV-1 transactivator of transcription (Tat) protein. We include recent findings on chromatin remodeling toward HIV transcription and its therapeutic implication is also discussed. The current status of small-molecular-weight compounds that affect HIV transcription is also described.

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Resveratrol inhibited Tat-induced HIV-1 LTR transactivation via NAD+-dependent SIRT1 activity

Cited by 51 publications

References 35 publications

Sirtuin modulators: an updated patent review (2012 – 2014)

Sirtuin modulators: an updated patent review (2012 – 2014)

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

Transcriptional Control of HIV Replication by Multiple Modulators and Their Implication for a Novel Antiviral Therapy

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