TNF and TNF Receptor Superfamily Members in HIV infection: New Cellular Targets for Therapy?

Figure 4

Potential TNF-based therapies to reactivate HIV-1 from latency. During HIV-1 latency, nuc-1 nucleosome is hypoacetylated. CTIP-2 interacts with Sp1, switching nuc-1 from transcriptionally active to a repressive state. Furthermore, CTIP-2 recruits HDACs that deacetylate the nuc-1 nucleosome. SUV39H1 adds trimethylation mark onto the histone protein H3. Furthermore, HP1 protein stabilizes the nuc-1 in transcriptionally silent state. The combination of TNF-alpha with HDACIs or HMTIs can disrupt the HIV-1 latency. TNF-alpha and HDACIs can trigger the activation of transcriptional activators, such as NF-kappaB (p50/p65 heterodimer). HDACIs may prevent the formation of heterochromatin, resulting in nuc-1 hyperacetylation and remodeling, thereby alleviating the HIV transcriptional block. The use of TNF, HDACIs, and HMTIs enhances HIV-1 LTR transcription and could participate in the clearance of HIV-1 from cellular reservoirs and ultimately could lead to the cure of HIV-infected patients.