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Updated: Jun 12, 2026

Evaluation of the Efficacy And Toxicity of RNAs Targeting HIV-1 Production for Use in Gene or Drug Therapy
Published on: September 5, 2016
Nicotinamide phosphoribosyltransferase/sirtuin 1 pathway is involved in human immunodeficiency virus type 1
Hong-Sheng Zhang1, Wei-Wei Sang, Yu-Ou Wang
1College of Life Science & Bioengineering, Beijing University of Technology, Pingleyuan 100#, District of Chaoyang, Beijing 100124, China. zhanghs@bjut.edu.cn
Abstract:
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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