Latent HIV in primary T lymphocytes is unresponsive to histone deacetylase inhibitors.
Latent HIV in primary T lymphocytes is unresponsive to histone deacetylase inhibitors.
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DOI：
10.1186/1743-422x-8-400
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发表时间：
2011-08-12
期刊：
影响因子：
4.8
通讯作者：
Cloyd MW
中科院分区：
文献类型：
--
作者：
Sahu GK;Cloyd MW
最近，人们对抗HIV治疗领域产生了相当大的兴趣，以识别和开发染色质修饰组蛋白脱乙酰酶（HDAC）抑制剂，可以有效地重新激活患者体内潜伏的HIV。希望这将有助于消除携带潜伏艾滋病毒的细胞，并最终治愈病毒。然而，尽管这些药物在HIV潜伏期的细胞系模型中显示出相关效力，但这些药物如何有效地刺激静止的原代CD4 T细胞中的潜伏HIV尚不清楚。在这里，我们表明，HDAC抑制剂丙戊酸（VPA）和阿司他丁A（TSA）是无法重新激活HIV潜伏感染的主要CD4 T细胞中产生的H80共培养系统。这引起了一种担忧，即单独抑制HDAC功能的药物可能不足以刺激患者静息CD4 T细胞中的潜伏HIV，并且不能实现潜伏储库库的任何预期减少。
Recently, there is considerable interest in the field of anti-HIV therapy to identify and develop chromatin-modifying histone deacetylase (HDAC) inhibitors that can effectively reactivate latent HIV in patients. The hope is that this would help eliminate cells harboring latent HIV and achieve an eventual cure of the virus. However, how effectively these drugs can stimulate latent HIVs in quiescent primary CD4 T cells, despite their relevant potencies demonstrated in cell line models of HIV latency, is not clear. Here, we show that the HDAC inhibitors valproic acid (VPA) and trichostatin A (TSA) are unable to reactivate HIV in latently infected primary CD4 T cells generated in the H80 co-culture system. This raises a concern that the drugs inhibiting HDAC function alone might not be sufficient for stimulating latent HIV in resting CD4 T cells in patients and not achieve any anticipated reduction in the pool of latent reservoirs.