Fig. 1

Epigenetic manipulation to eradicate HIV: “shock and kill” or “block and lock”? a Latent HIV provirus-established reservoirs in infected resting CD4+ memory T cells and myeloid cells are not eliminated by cART and are thus prone to be reactivated after cART discontinuation. One strategy to eliminate those reservoirs is the “shock and kill” therapy. b Shock-inducer agents like histone deacetylase (HDAC), DNA, or histone methyltransferase (DNMT and HMT respectively) inhibitors used alone or in combination with other players (PKC agonists, P-TEFb releasing agents, TNF, TPA) could reverse latency through the removal of repressive silencing marks imposed on the nucleosome Nuc-1 or the DNA. This purges the viral reservoirs and leads eventually to the clearance of virus-harboring cells along with cART. On the other hand (c), blocking Tat, a viral protein indispensable for the recruitment of transcriptional factors like the positive transcription elongation factor B (P-TEFb), by a latency inducing reagent such as dCA reduces viral transcription and locks the HIV promoter in a super-latency state resistant to any reactivation stimuli leading potentially to a functional cure