Histone deacetylase inhibitors and HIV latency
Year: 2010
Type: review
Abstract: PURPOSE OF REVIEW: Interest has re-emerged in approaches to eradicate HIV infection. A series of modifications of nucleosomal histones within chromatin are a key mechanism of HIV gene regulation that alters the recruitment of transcription factors to viral DNA. The balance of these histone modifications in the vicinity of the HIV LTR plays an important role in the maintenance of proviral quiescence in rare latently infected cells, and presents a target for therapies aimed at purging this reservoir of persistent HIV infection. RECENT FINDINGS: Altering the balance of acetylase and deacetylase activity within CD4+ lymphocytes using histone deacetylase (HDAC) inhibitors, or other epigenetic drugs, has recently emerged as a promising approach to purge the reservoir of persistent infection. Multiple molecular mechanisms appear to underlie the establishment and maintenance of persistent, latent HIV infection, most frequently in the resting central memory CD4+ T cell. HDAC inhibitors perturb this balance, induce expression of integrated provirus, and may allow attack of this primary form of persistent HIV infection. SUMMARY: Although HDAC inhibitors are a promising approach, a better understanding of relevant mechanisms of latency in vivo, and better tools to translate this knowledge into therapies are needed.
Source: Current Opinion in HIV and AIDS
Author: David M Margolis
Institution: University of North Carolina at Chapel Hill
Language: English
Topic: HIV Research and Treatment
Subfield: Virology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: green
Funders: Georgia Clinical and Translational Science Alliance, National Institutes of Health, National Institute of Mental Health, National Institute on Drug Abuse, National Institute of Allergy and Infectious Diseases, National Center for Research Resources, Center for AIDS Research, University of North Carolina at Chapel Hill
Awards: Innovative therapies to elimate persistent HIV Infection, Nanocrystal delivery to the CNS to improve HIV therapy, UNC Clinical and Translational Science Award, G68625873, G7477205992, G7817696117, The University of North Carolina Center for AIDS Research, HIV Latency, Epigenetics, and Therapeutics
OpenAlex ID: W2086674142