Structure of retroviral LTRs. Retroviral LTRs are divided into the U3, R, and U5 regions, and the U3 region is further divided into the Modulatory, Enhancer (E) and Promoter regions (top bars). HIV-1, HIV-2, and SIV all contain highly conserved promoters containing TATA boxes (yellow) and Sp factor binding sites (red) and enhancers (labeled E in light blue bar) containing NF-κB binding sites (blue). The R region of each contains a trans-acting responsive element (TAR) (orange) that forms an RNA stem loop structure upon transcription that binds to the viral protein Tat. A negative regulatory element (NRE, pink) was identified that was subsequently shown to serve as both activator and repressor by binding NFAT proteins (dark blue), AP-1 proteins (purple), and C/EBP factors (green). The modulatory regions of SIVmac and HIV-2 also contain purine box arrays (PuB, gold) and sites that bind members of the Ets family (teal).