Nicotinamide Phosphoribosyltransferase/Sirtuin 1 Pathway Is Involved in Human Immunodeficiency Virus Type 1 Tat-Mediated Long Terminal Repeat Transactivation

作者：Zhang, Hong-Sheng^*; Sang, Wei-Wei; Wang, Yu-Ou; Liu, Wei

来源：Journal of Cellular Biochemistry, 2010, 110(6): 1464-1470.

DOI：10.1002/jcb.22704

• TAT
• SIRT1
• NAMPT
• LTR TRANSACTIVATION
• HIV-1

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. J. Cell. Biochem. 110: 1464-1470, 2010.

• 出版日期2010-8-15
• 单位北京工业大学