Figure 3.

Pharmaceutical approaches of the potential reactivation pathways on latently integrated HIV-1 genome. Multiple ways of reactivation are possible to occur to re-initiate the HIV-1 transcription. Extern signals, such as TNF-α, can trigger the activation of transcriptional activator, like the heterodimer p50/p65. In the mean time, host protein balance may change, leading to higher availability of transcriptional activators. For instance, miRNAs regulates the rate of PCAF, a coactivator produced by the host cell (green arrow - Multiple potential reactivation pathways). There are some critical steps in this process that may be targeted to reactivate or hinder the latency establishment (Red boxes). HDAC inhibitors (HDACi) may prevent the formation of heterochromatin; Prostratin induces the IKK activation, which provokes the activation of transcriptions factors; HMBA increases the pTEFb release from the inactive stock; it is possible to reverse the miRNAs negative impact on the mRNAs of transcriptional activators and/or CycT1 through specific siRNAs.