Regulation of HIV-1 transcription in differentiated macrophages. In differentiated macrophages, NF-κB and NFAT are constitutively localized in the nucleus; however, in the presence of large amounts of NF-κB, NFAT is unable to bind the LTR. NF-κB-Sp1 protein-protein interactions bind the LTR cooperatively and activate transcription synergistically in response to cellular stimuli. Sp sites are necessary for viral replication, and the ratio of Sp1 proteins to Sp3 proteins increases, thus increasing transcription of the virus. As the cell matures, C/EBPα levels decrease and C/EBPβ and C/EBPδ levels increase. AP-1 is constitutively expressed but loses its ability to bind to the LTR. Tat binds to the transactivation response region (TAR) structure on the viral RNA and recruits (P-TEFb (the Cyclin dependent kinase 9 (Cdk9) and cyclin T1 (CycT1) complex) through binding to cyclin T1. Recruitment of P-TEFb to TAR induces hyperphosphorylation of CTD by Cdk9, thereby enhancing the transcriptional elongation of HIV-1.