Journal article
Histone deacetylase inhibitor romidepsin inhibits De Novo HIV-1 infections
KL Jønsson, M Tolstrup, J Vad-Nielsen, K Kjær, A Laustsen, MN Andersen, TA Rasmussen, OS Søgaard, L Østergaard, PW Denton, MR Jakobsen
Antimicrobial Agents and Chemotherapy | AMER SOC MICROBIOLOGY | Published : 2015
DOI: 10.1128/AAC.00574-15
Abstract
Adjunct therapy with the histone deacetylase inhibitor (HDACi) romidepsin increases plasma viremia in HIV patients on combination antiretroviral therapy (cART). However, a potential concern is that reversing HIV latency with an HDACi may reactivate the virus in anatomical compartments with suboptimal cART concentrations, leading to de novo infection of susceptible cells in these sites. We tested physiologically relevant romidepsin concentrations known to reactivate latent HIV in order to definitively address this concern. We found that romidepsin significantly inhibited HIV infection in peripheral blood mononuclear cells and CD4+ T cells but not in monocyte-derived macrophages. In addition, ..
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Awarded by Danish Strategic Research Council
Awarded by Danish Research Council
Funding Acknowledgements
This study was supported in part by the Lundbeck Foundation (K.L.J. and M.R.J.), Aarhus University Research Foundation (M.R.J.), Danish Strategic Research Council grant 0603-00521B (L.O.), and Danish Research Council grant 12-133887 (O.S.S.). The funders had no role in study design, data collection, and analysis, decision to publish, or writing of the manuscript. The following reagents were obtained through the NIH AIDS Reagent Program, Division of AIDS, NIAID, NIH: TZM-bl cells (John C. Kappes, Xiaoyun Wu, and Tranzyme, Inc.), ACH-2 cells (Thomas Folks), and MOLT-4/CCR5 cells (Masanori Baba, Hiroshi Miyake, and Yuji Iizawa).