...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>AIDS >Histone methyltransferase inhibitors induce HIV-1 recovery in resting CD4+ T cells from HIV-1-infected HAART-treated patients
【24h】

Histone methyltransferase inhibitors induce HIV-1 recovery in resting CD4+ T cells from HIV-1-infected HAART-treated patients

机译：组蛋白甲基转移酶抑制剂诱导HIV-1感染的HAART治疗患者的静息CD4 + T细胞中的HIV-1恢复

获取原文
获取原文并翻译 | 示例
   

获取外文期刊封面封底 >>

       
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Objective: Reactivation of HIV-1 expression in persistent reservoirs together with an efficient HAART has been proposed as an adjuvant therapy aimed at reaching a functional cure for HIV. Previously, H3K9 methylation was shown to play a major role in chromatin-mediated repression of the HIV-1 promoter. Here, we evaluated the therapeutic potential of histone methyltransferase inhibitors (HMTIs) in reactivating HIV-1 from latency. Design: We evaluated the reactivation potential of two specific HMTIs (chaetocin and BIX-01294, two specific inhibitors of Suv39H1 and G9a, respectively) in ex-vivo cultures of resting CD4 + T cells isolated from HIV-1-infected HAART-treated individuals. Methods: We measured HIV-1 recovery in ex-vivo cultures treated with an HMTI alone or in combination with other HIV-1 inducers (in absence of IL-2 and of allogenic stimulation) of CD8 +-depleted peripheral blood mononuclear cells (PBMCs) or of resting CD4 + T cells isolated from 67 HIV-infected, HAART-treated patients with undetectable viral load. Results: We demonstrated, for the first time, that chaetocin induced HIV-1 recovery in 50% of CD8-depleted PBMCs cultures and in 86% of resting CD4 + T-cell cultures isolated from HIV-1-infected, HAART-treated patients, whereas BIX-01294 reactivated HIV-1 expression in 80% of resting CD4 + T-cell cultures isolated from similar patients. Moreover, we showed that combinatory treatments including one HMTI and either the histone deacetylase inhibitor suberoylanilide hydroxamic acid or the non-tumor-promoting NF-κB inducer prostratin had a higher reactivation potential than these compounds alone. Conclusion: Our results constitute a proof-of-concept for the therapeutic potential of HMTIs in strategies aiming at reducing the pool of latent reservoirs in HIV-infected, HAART-treated patient.
机译：目的：活化持久性水库中HIV-1表达的活化以及有效的HAART已被提议作为辅助疗法，旨在实现对HIV的功能性治愈。以前，H3K9甲基化被证明在染色质介导的HIV-1启动子阻遏中起主要作用。在这里，我们评估了组蛋白甲基转移酶抑制剂（HMTIs）从潜伏期重新激活HIV-1的治疗潜力。设计：我们评估了从HIV-1感染的HAART治疗个体中分离得到的静息CD4 + T细胞的离体培养物中两种特异性HMTI（分别是chaetocin和BIX-01294，Suv39H1和G9a的两种特异性抑制剂）的再激活潜力。 。方法：我们测量了单独用HMTI或与其他HIV-1诱导剂（不存在IL-2和同种异体刺激）组合用CD8 +耗尽的外周血单个核细胞（PBMC）处理的离体培养物中HIV-1的回收率）或从67例经HIV感染，经HAART治疗的病毒载量无法检测的患者中分离出的静息CD4 + T细胞。结果：我们首次证明，壳聚糖诱导了50％的CD8耗尽的PBMC培养物和86％的静息CD4 + T细胞培养物中HIV-1的恢复，这些培养物是从HIV-1感染的，接受HAART治疗的患者中分离的，而BIX-01294重新激活了从相似患者中分离出的80％的静息CD4 + T细胞培养物中的HIV-1表达。此外，我们表明，包括一种HMTI和组蛋白脱乙酰基酶抑制剂亚磺酰苯胺异羟肟酸或非肿瘤促进性NF-κB诱导性雌激素的联合治疗比单独使用这些化合物具有更高的活化潜力。结论：我们的结果构成了HMTIs治疗潜力的概念验证，该策略旨在减少HIV感染的HAART治疗患者的潜伏储库。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号