Histone deacetylase inhibitors butyrate and bufexamac inhibitde novoHIV-1 infection in CD4 T-cells

Abstract

AbstractWhile current combined antiretroviral therapy (cART) allows control of HIV replication in patients and effectively suppresses plasma viral loads, it is unable to target latent reservoirs, which are responsible for virus rebound after discontinuation of therapy. Several histone deacetylase inhibitors (HDACIs) have been shown to target reservoirs and to reactivate latent HIV. While this effect is highly desired, it carries the risk that HIV-1 may be reactivated in tissue compartments were cART concentrations are insufficient and thus leading tode novoinfections in this sites. To address this concern, we evaluated the effect of different HDACIs for their ability to reverse HIV latency and to modulatede novoinfections. Two of the inhibitors, sodium butyrate and bufexamac, significantly inhibitedde novoHIV-1 infection in activated CD4+T-cells. Transcriptome and proteome analysis indicated global changes of protein abundancies, exhibited reduced proliferation of CD4+T-cells, and revealed butyrate-based proteasomal degradation of EP300, an important factor for HIV-1 replication. Our results disclose new potential treatment strategies and minimizes the concern of potential reservoir reseeding by HDACIs.