MicroRNAs　(miRNAs)　are　small　non-coding　RNAs　that　regulate　gene　expression　and　may　contribute　to　the　development　and　progression　of　many　infective　diseases　including　human　immunodeficiency　virus　1　(HIV-1)　infection.　The　Tat　protein　is　fundamental　to　viral　gene　expression.　In　this　study,　our　goal　was　to　investigate　the　regulation　of　a　specific　miRNA　(known　as　miR-217)　in　multinuclear　activation　of　galactosidase　indicator　(MAGI)　cells　and　explore　the　mechanisms　by　which　miR-217　influenced　Tat-induced　HIV-1　transactivation　through　down-regulation　of　SIRT1　expression.　We　showed　that　miR-217　was　up-regulated　when　Tat　was　expressed　in　multinuclear　activation　of　galactosidase　indicator　cells.　Forced　expression　of　＂miR-217　mimics＂　increased　Tat-induced　LTR　transactivation.　In　addition,　miR-217　significantly　inhibited　SIRT1　protein　expression　by　acting　on　the　3＇-UTR　of　the　SIRT1　mRNA.　In　turn,　the　decrease　in　SIRT1　protein　abundance　provoked　by　miR-217　affected　two　important　types　of　downstream　signaling　molecules　that　were　regulated　by　Tat.　Lower　expression　of　SIRT1　caused　by　miR-217　enhanced　Tat-induced　phosphorylation　of　IKK　and　p65-NRB　and　also　exacerbated　the　loss　of　AMPK　phosphorylation　triggered　by　Tat.　Our　results　uncover　previously　unknown　links　between　Tat　and　a　specific　host　cell　miRNA　that　targets　SIRT1.　We　also　demonstrate　that　this　regulatory　mechanism　impinges　on　p65-NEkB　and　AMPK　signaling:　two　important　host　cell　pathways　that　influence　HIV-1　pathogenesis.　Our　results　also　suggest　that　strategies　to　augment　SIRT1　protein　expression　by　down-regulation　of　miR-217　may　have　therapeutic　benefits　to　prevent　HIV-1　replication.　(C)　2012　Elsevier　B.V.　All　rights　reserved.