<p>(<b>A</b>) In absence of cocaine or HIV miR155 targets DC-SIGN and PU.1, reducing the expression post-transcriptionally. Lowered PU.1 and DC-SIGN expression is observed in mature DCs. (<b>B</b>) In the presence of Cocaine or HIV alone miR-155 levels are reduced resulting in elevated PU.1 and DC-SIGN expression. This phenotype is evident in immature DCs (iDCs). Together HIV and cocaine, synergize to dramatically lower miR-155 resulting in elevated levels of the transcription factor Pu.1. In turn, Pu.1 binds sites within the DC-SIGN promoter as well as the HIV LTR and promotes transcription. The resulting elevated DC-SIGN expression in DCs lead to maintenance an immature DC phenotype and thus increased HIV infectivity. By binding NF-κB sites within the LTR, PU.1 increases viral transcription and pathogenesis.</p