Effect of Iron Chelators on HIV‐1 transcription

HIV‐1 Tat protein activates viral gene expression by recruiting transcriptional co‐activators including CDK9/cyclin T1, which phosphorylates the C‐terminal domain (CTD) of RNA Polymerase II (RNAPII). Our recent studies indicate that cell‐cycle‐dependent kinase 2 (CDK2) is required for Tat‐dependent transcription. We utilized the iron chelators, 311 that was previously shown to inhibit CDK2 expression, and ICL670 to chelate intracellular iron. We analyzed the effect of the iron chelators on HIV‐1 transcription using HeLa‐MAGI cells and CEM‐GFP cells containing an integrated HIV‐1 LTR that were infected with adenovirus expressing HIV‐1 Tat protein. Iron depletion by 311 or ICL670 inhibited Tat‐induced HIV‐1 transcription, most profoundly in CEM‐GFP cells. Treatment of CEM‐GFP and HeLa MAGI cells with iron chelators decreased CDK9 protein level, and to a lesser extent decreased CDK2 protein level. Our findings provide evidence that iron chelators may inhibit HIV‐1 transcription apparently by affecting expression of CDK9 and CDK2.