SIRT1 regulates Tat-induced HIV-1 transactivation through activating AMP-activated protein kinase

Zhang, Hongsheng; Wu, Meng-Ran

doi:10.1016/j.virusres.2009.08.005

Cited by 49 publications

(44 citation statements)

References 42 publications

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“…A number of recent reports have described other interactions between viruses and AMPK: The HIV-1 Tat protein has been reported to inhibit AMPK, and, consistent with this effect, AMPK agonists inhibited Tat transactivation of the HIV-1 LTR (35). Infection with human cytomegalovirus (36) also resulted in an inhibition of AMPK T172 phosphorylation.…”

Section: Discussionmentioning

confidence: 81%

Enhanced hepatitis C virus genome replication and lipid accumulation mediated by inhibition of AMP-activated protein kinase

Mankouri

Tedbury

Gretton

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

133

145

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Hepatitis C virus (HCV) infection is associated with dysregulation of both lipid and glucose metabolism. As well as contributing to viral replication, these perturbations influence the pathogenesis associated with the virus, including steatosis, insulin resistance, and type 2 diabetes. AMP-activated protein kinase (AMPK) plays a key role in regulation of both lipid and glucose metabolism. We show here that, in cells either infected with HCV or harboring an HCV subgenomic replicon, phosphorylation of AMPK at threonine 172 and concomitant AMPK activity are dramatically reduced. We demonstrate that this effect is mediated by activation of the serine/ threonine kinase, protein kinase B, which inhibits AMPK by phosphorylating serine 485. The physiological significance of this inhibition is demonstrated by the observation that pharmacological restoration of AMPK activity not only abrogates the lipid accumulation observed in virus-infected and subgenomic replicon-harboring cells but also efficiently inhibits viral replication. These data demonstrate that inhibition of AMPK is required for HCV replication and that the restoration of AMPK activity may present a target for much needed anti-HCV therapies.

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Section: Discussionmentioning

confidence: 81%

Enhanced hepatitis C virus genome replication and lipid accumulation mediated by inhibition of AMP-activated protein kinase

Mankouri

Tedbury

Gretton

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

133

145

View full text Add to dashboard Cite

show abstract

“…(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]. In this study, we have shown that Tat activation is associated with SIRT1 activity.…”

Section: Nadmentioning

confidence: 73%

“…All immunoblots were visualized using the Odyssey infrared imaging system (LI-COR Biosciences) and secondary Abs according to the manufacturer's instructions. When using the infrared dye-labeled secondary antibody, the membranes were scanned directly after incubation and the band intensities were quantified using the Odyssey infrared imaging system (Li-Cor Biosciences) [Zhang and Wu, 2009].…”

Section: Immunoblot Analysismentioning

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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“…The role of SIRT1 in controlling HIV-1 silencing and transactivation has been controversial (Pagans et al, 2005; Pinzone et al, 2013; Zhang and Wu, 2009). To verify that SCFAs downregulation of SIRT1 contributes to HIV-1 induction, we infected 2D10 cells with lentiviruses expressing five different SIRT1-pecific shRNAs and a control shRNA.…”

Section: Resultsmentioning

confidence: 99%

“…Multiple studies have demonstrated that HIV-1 Tat protein is a substrate of SIRT1 for deacetylation and functional inhibition or knockdown of SIRT1 is known to enhance Tat’s ability to transactivate HIV-1 (Pinzone et al, 2013; Zhang et al, 2010; Zhang and Wu, 2009). By contrast, in SIRT1-null mouse cells, where there is no SIRT1 expression, Tat transactivation is defective but can be rescued by expression of SIRT1 (Pagans et al, 2005).…”

Section: Discussionmentioning

confidence: 99%

Short chain fatty acids potently induce latent HIV-1 in T-cells by activating P-TEFb and multiple histone modifications

Das¹,

Dobrowolski²,

Shahir³

et al. 2015

Virology

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HIV patients with severe periodontitis have high levels of residual virus in their saliva and plasma despite effective therapy (HAART). Multiple short chain fatty acids (SCFAs) from periodontal pathogens reactivate HIV-1 in both Jurkat and primary T-cell models of latency. SCFAs not only activate positive transcription elongation factor b (P-TEFb), which is an essential cellular cofactor for Tat, but can also reverse chromatin blocks by inducing histone modifications. SCFAs simultaneously increase histone acetylation by inhibiting class-1/2 histone deacetylases (HDACs) and decrease repressive histone tri-methylation at the proviral LTR by downregulating expression of the class-3 HDAC sirtuin-1 (SIRT1), and the histone methyltransferases enhancer of Zeste homolog 2 (EZH2) and suppressor of variegation 3–9 homolog 1 (SUV39H1). Our findings provide a mechanistic link between periodontal disease and enhanced HIV-1 replication, and suggest that treatment of periodontal disease, or blocking the activities of SCFAs, will have a therapeutic benefit for HIV patients.

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SIRT1 regulates Tat-induced HIV-1 transactivation through activating AMP-activated protein kinase

Cited by 49 publications

References 42 publications

Enhanced hepatitis C virus genome replication and lipid accumulation mediated by inhibition of AMP-activated protein kinase

Enhanced hepatitis C virus genome replication and lipid accumulation mediated by inhibition of AMP-activated protein kinase

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

Short chain fatty acids potently induce latent HIV-1 in T-cells by activating P-TEFb and multiple histone modifications

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