Histone Deacetylase Inhibitor Romidepsin Inhibits De Novo HIV-1 Infections
| Autor: | Martin Tolstrup, Morten Andersen, Paul W. Denton, Ole Schmeltz Søgaard, Martin R. Jakobsen, Thomas A Rasmussen, Kathrine Kjær, Anders Laustsen, Lars Østergaard, Kasper L Jønsson, Johan Vad-Nielsen |
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| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
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CD4-Positive T-Lymphocytes medicine.drug_class Cell Survival T cell Primary Cell Culture Viremia HIV Infections Biology Virus Replication Peripheral blood mononuclear cell Antiviral Agents Virus Monocytes Romidepsin Interferon-gamma Depsipeptides medicine Humans Pharmacology (medical) Cell Proliferation Pharmacology Histone deacetylase inhibitor virus diseases medicine.disease Virus Latency Histone Deacetylase Inhibitors Infectious Diseases medicine.anatomical_structure Cell culture Immunology Cancer research HIV-1 medicine.drug |
| Zdroj: | Jønsson, K L, Tolstrup, M, Vad-Nielsen, J, Kjær, K, Laustsen, A, Andersen, M N, Rasmussen, T A, Søgaard, O S, Østergaard, L J, Denton, P W & Jakobsen, M R 2015, ' Histone Deacetylase Inhibitor Romidepsin Inhibits de novo HIV-1 Infections ', Antimicrobial Agents and Chemotherapy, vol. 59, no. 7, pp. 3984-3994 . https://doi.org/10.1128/AAC.00574-15 |
| DOI: | 10.1128/AAC.00574-15 |
| Popis: | 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, romidepsin impaired HIV spreading in CD4 + T cell cultures. When we evaluated the impact of romidepsin on quantitative viral outgrowth assays with primary resting CD4 + T cells, we found that resting CD4 + T cells exposed to romidepsin exhibited reduced proliferation and viability. This significantly lowered assay sensitivity when measuring the efficacy of romidepsin as an HIV latency reversal agent. Altogether, our data indicate that romidepsin-based HIV eradication strategies are unlikely to reseed a latent T cell reservoir, even under suboptimal cART conditions, because romidepsin profoundly restricts de novo HIV infections. |
| Databáze: | OpenAIRE |
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