Epigenetics of HIV infection: promising research areas and implications for therapy.

We surveyed current trends in epigenetics in general and epigenetics of HIV infection and AIDS in particular to pinpoint promising areas for translational research. Epigenetic mechanisms mark and affect the structure of chromatin, thereby controlling the activity of promoters. Because epigenetic changes are reversible, epigenetic drugs can be used to modulate gene activity. At present, silenced HIV genomes, the latent HIV reservoir, is a major obstacle for a curative treatment of AIDS patients. Epigenetic therapy aims at the purging of the latent reservoir by switching on transcription of silent HIV genomes. The basic idea is that the cytopathic effect of the replicating virus and the immune system may eliminate the reactivated cells, whereas HAART may block the infection of new target cells. Although current efforts concentrate on long-lived resting memory CD4+ T-cells, dormant HIV proviruses also reside in other cell types. Thus, epigenetic characterization of the various HIV-infected host cells and host cell-dependent HIV latency mechanisms is a promising research area and may facilitate the development of cell type-specific epigenetic drugs. HAART itself affects the epigenotype of host cells. This may contribute to the development of drug resistance and unwanted side effects. A pharmacoepigenetic approach may help to elucidate and revert such phenomena. In addition to latent reservoir purging, epigenetic research offers alternative therapeutic tools as well; although not aimed at the elimination of the virus, targeted silencing of HIV transcription by epigenetic regulators may help HAART to minimize virus replication.