It has been demonstrated that Tat triggers KSHV reactivation from latency (Harrington et al., 1997; Zeng et al., 2007) and also accelerates tumor progression induced by KSHV-encoded oncoproteins such as G protein-coupled receptor and kaposin A. In addition to Tat, accessory negative factor (Nef) is another early HIV-1-encoded regulatory protein that is an enforcing factor in the pathogenesis of HIV/AIDS and it can penetrate KSHV vIL-6-expressing endothelial cells. Here, TAT is linked to AIDS.