Schematic of the pathway triggered by Tat and leading to activation of ISGs by Tat in APCs infected by HIV. (A) Tat triggers signaling pathways that activate ISGs by associating with MAP2K3 and MAP2K6 kinases, which in turn activate p38 MAPK and STAT1, and with IRF7 in APCs infected by HIV. (B) Activation of MAP2K3, MAP3K6, and IRF7 leads to expression of many ISGs (shown here in connection with MAP2K3, MAP3K6, and IRF7), whose product can positively impact T-cell immunoactivation and negatively impact virus production. Bold labeling indicates genes found upregulated by HIV and Tat in APC (Figures 4,5).^8,9