Histone deacetylase inhibitor MC1293 induces latent HIV-1 reactivation by histone modification in vitro latency cell lines.

Histone deacetylase inhibitor MC1293 induces latent HIV-1 reactivation by histone modification in vitro latency cell lines.
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DOI:
10.2174/1570162x11311010004
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发表时间:
2013
影响因子:
1
通讯作者:
Xiying Qu;H. Ying;Xiaohui Wang;Chuijin Kong;Xin Zhou;Pengfei Wang;Huanzhang Zhu
Xiying Qu;H. Ying;Xiaohui Wang;Chuijin Kong;Xin Zhou;Pengfei Wang;Huanzhang Zhu
中科院分区:
医学4区
文献类型:
--
作者:
Xiying Qu;H. Ying;Xiaohui Wang;Chuijin Kong;Xin Zhou;Pengfei Wang;Huanzhang Zhu

文献摘要

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HIV-1潜伏期仍然是根除感染者体内病毒的一个主要问题。我们评估了MC1293对HIV-1 LTR的表观遗传变化和潜伏病毒在潜伏Jurkat T细胞系中的诱导作用。我们发现MC1293可以激活HIV-1基因表达,增加HIV-1 LTR nuc-1位点H3和H4的乙酰化水平,并且MC1293可以与prostratin协同激活HIV-1启动子,与Trichostatin A (TSA)相比具有相对较低的毒性。结果表明,组蛋白乙酰化在调节HIV-1 LTR基因表达中起重要作用,MC1293是抗潜伏期治疗的潜在候选药物。
HIV-1 latency remains a major problem for the eradication of viruses in infected individuals. We evaluated the effect of MC1293 on the epigenetic change at HIV-1 LTR and the induction of the latent viruses in the latency Jurkat T cell line. We found MC1293 can activate HIV-1 gene expression, increase the acetylation level of H3 and H4 at the nuc-1 site of HIV-1 LTR. In addition, MC1293 can synergize with prostratin to activate the HIV-1 promoter, and has relatively lower toxicity compared to Trichostatin A (TSA). The results suggest that the acetylation of histone plays an important role in regulating HIV-1 LTR gene expression, and MC1293 is potential drug candidate for antilatency therapies.