Tat＇s　transactivating　activity　is　controlled　by　sirtuin　1　(SIRT1)　that　connects　HIV　transcription　with　the　metabolic　state　of　the　cell.　Nicotinamide　phosphoribosyltransferase　(NAMPT)　is　a　key　enzyme　in　the　salvaging　pathway　for　the　synthesis　of　nicotinamide　adenine　dinucleotide　(NAD(+))　that　is　involved　in　energy　metabolism.　Host　encoded　microRNAs　(miRNAs)　may　influence　viral　replication.　In　this　study,　our　goal　was　aimed　to　investigate　the　regulation　of　miR-182　in　TZM-bl　cells　and　explore　the　mechanisms　by　which　miR-182　influenced　Tat-induced　HIV-1　transactivation　through　targeting　at　down-regulation　of　NAMPT　expression.　We　showed　that　miR-182　was　up-regulated　when　Tat　was　expressed　in　T2M-bl　cells.　MiR-182　significantly　inhibited　NAMPT　protein　expression　by　acting　on　the　3＇-UTR　of　the　NAMPT　mRNA.　MiR-182　was　involved　in　Tat-induced　NAD(+)　depletion,　down-regulation　of　SIRT1　protein　expression　and　activity,　increased　acetylation　of　p65.　Forced　expression　of　＂miR-182　mimics＂　increased　Tat-induced　LTR　transactivation.　Our　results　uncover　previously　unknown　links　between　Tat　and　a　specific　host　cell　miRNA　that　targets　NAMPT.　Our　results　suggest　that　strategies　to　augment　NAMPT　protein　expression　by　down-regulation　of　miR-182　may　have　therapeutic　benefits　to　prevent　HIV-1　replication.　(C)　2012　Elsevier　Ltd.　All　rights　reserved.