FIG 11.

Hypothetical model depicting a concentration-dependent switch of the Tat protein through differential PTMs that mutually serve as an activator or suppressor at different phases of viral transcription. The model suggests that the diverse PTMs of Tat play a critical role in permitting the transactivator to toggle between being an activator and being a suppressor of the transactivation of the LTR. At the time of commitment to latency, the intracellular concentrations of Tat are not limiting. Tat may initiate a negative feedback response of viral transcription in a concentration-dependent manner by regulating the expression of host factors that control the PTM(s) of Tat. The negative feedback effect of Tat therefore follows its initial positive feedback on the viral promoter. A viral promoter characterized by stronger transcriptional activity thus mediates the establishment of latency at a higher rate by producing more Tat. The data presented in this work are consistent with this model.