Administration of HDAC inhibitors to reactivate HIV-1 expression in latent cellular reservoirs: implications for the development of therapeutic strategies.
The discovery of powerful antiviral compounds in the 90's raised the hope that the human immunodeficiency virus type 1 (HIV-1) might be eradicated. However, if these drugs succeed in decreasing and controlling viral replication, complete eradication of the virus is nowadays impossible. The persistence of virus even after long periods of highly active antiretroviral therapy (HAART) mainly results from the presence of cellular reservoirs that contain transcriptionally competent latent viruses capable of producing infectious particles after cellular activation. These latently infected cells are a permanent source for virus reactivation and lead to a rebound of the viral load after interruption of HAART. Activation of HIV gene expression in these cells combined with an effective HAART has been proposed as an adjuvant therapy that could lead to the elimination of the latently infected cells and then to the eradication of the infection. In this context, we have previously demonstrated that deacetylase inhibitors (HDACi) synergize with TNF-induced NF-kappaB to activate the HIV-1 promoter. The physiological relevance of the TNF/HDACi synergism was shown on HIV-1 replication in both acutely and latently HIV-infected cell lines. Based on these results, we propose the administration of deacetylase inhibitor(s) together with continuous HAART as a new potential therapeutic perspective to decrease the pool of latent HIV reservoirs by forcing viral expression.
Laboratoire de Virologie Moléculaire, Service de Chimie Biologique rue des Profs Jeener et Brachet 12, Institut de Biologie et de Médecine Moléculaires, Université Libre de Bruxelles, 6041 Gosselies, Belgium.
Dominique
D
Demonté
Vincent
V
Quivy
Yves
Y
Colette
Carine
C
Van Lint
D019380:Anti-HIV Agents / Q000494:pharmacology* / Q000627:therapeutic use; D023241:Antiretroviral Therapy, Highly Active; D004791:Enzyme Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D015967:Gene Expression Regulation, Viral; D015658:HIV Infections / Q000188:drug therapy; D015497:HIV-1 / Q000187:drug effects* / Q000502:physiology; D056572:Histone Deacetylase Inhibitors; D006801:Humans; D014779:Virus Replication / Q000187:drug effects*
D019380:Anti-HIV Agents; D004791:Enzyme Inhibitors; D056572:Histone Deacetylase Inhibitors