The Role Of MicroRNAs Related To SIRT1and NAMPT Regulates The Transcripitional Activation Of HIV-1TAT

The human immunodeficiency virus (HIV) is a primate lentivirus that causes theacquired immunodeficiency syndrome (AIDS). The regulatory genes of the HIV-1aretat and rev, encoding the proteins named Trans-activator of transcription (Tat). TheTat protein is absolutely required for virus replication since it controls thetranscription of the full-length viral mRNA, and it can cause apoptosis in cells. Tatplays a significant role in HIV-1life cycle，and it maybe become the novel target inanti-HIV research.In this study, microRNA was applied to interfer the expression of HIV-1regulatory genes. We selected some micoRNAs that relate to Silent mating typeinformation regulation2homolog1（SIRT1） and nicotinamide phosphotransferase(Nampt),which is tightly interrelated to SIRT1,to test that whether they can inhibitHIV-1transactivation.Results: We found that some microRNA indeed could play an important role ininhibiting Tat-mediated HIV-1LTR transcription. In those microRNAs the miR-34,miR-199a, miR-217all can regulate Tat-mediatede HIV-1LTR transactivationthrough inhibiting human histone deacetylase SIRT1. Nampt regulates the activity ofSIRT1through NAD~+level’s regulation. Nampt and NAD~+levels were tightlyrelated. As SIRT1is NAD~+-dependent, we selected the miR-182to verify thisexperiment. Facts proved that miR-182effectively reduced the protein expression ofNampt. Nampt and SIRT1were positively correlated. We also confirmed that miR-182effectively cut down SIRT1mRNA level and protein expression. ThesemicroRNAs effectively enhanced the acetylation nuclear factor NF-κB P65subunit’sprotein expression, the addition of acetylation P65subunit will lead to the activationof transcription which would promote HIV-1transcription. MicroRNAs inhibitorseffectively reduced the P65acetylation that lead to HIV transcription process hindered.The results show that it’s a feasible new treatment by looking for microRNA to anti-HIV-1therapy.