期刊
EBIOMEDICINE
卷 8, 期 -, 页码 217-229出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.ebiom.2016.04.019
关键词
HIV-1; Eradication; Latency reversal agents; Elite suppressors; Elite controllers; CD8+ T cells
资金
- Johns Hopkins University Center for AIDS Research [P30AI094189, 2R56AI080328-05A1, 1R01AI120024-01]
Shock and kill strategies involving the use of small molecules to induce viral transcription in resting CD4+ T cells (shock) followed by immune mediated clearance of the reactivated cells (kill), have been proposed as a method of eliminating latently infected CD4+ T cells. The combination of the histone deacetylase (HDAC) inhibitor romidepsin and protein kinase C (PKC) agonist bryostatin-1 is very effective at reversing latency in vitro. However, we found that primary HIV-1 specific CD8+ T cells were not able to eliminate autologous resting CD4+ T cells that had been reactivated with these drugs. We tested the hypothesis that the drugs affected primary CD8+ T cell function and found that both agents had inhibitory effects on the suppressive capacity of HIV-specific CD8+ T cells from patients who control viral replication without antiretroviral therapy (elite suppressors/controllers). The inhibitory effect was additive and multi-factorial in nature. These inhibitory effects were not seen with prostratin, another PKC agonist, either alone or in combination with JQ1, a bromodomain-containing protein 4 inhibitor. Our results suggest that because of their adverse effects on primary CD8+ T cells, some LRAs may cause immune-suppression and therefore should be used with caution in shock and kill strategies. (C) 2016 The Authors. Published by Elsevier B.V.
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