Nature：抗癌药物伏立诺他能够清出潜伏HIV病毒

marine0425030

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楼主：ipsvirus

来自美国北卡罗来纳大学教堂山分校等研究人员于2012年7月25日发表在《自然》期刊上的一篇开创性的研究论文，证实一种能够被用来治疗某些类型淋巴瘤的去乙酰化酶抑制剂药物---伏立诺他(vorinostat)---能够清出病人体内潜伏的HIV病毒。

尽管使用抗逆转录药物能很好的控制病毒的复制，但HIV能整合到宿主基因组中进入休眠状态逃逸宿主免疫及药物攻击是治愈艾滋病的一个主要障碍。组蛋白去乙酰化酶抑制剂药物---伏立诺他(vorinostat)已被报道在体外实验中能够破坏IV的潜伏状态，使HIV暴露，但这种效果在临床上还没有得到验证。因此研究人员开展一系列实验来评价这种药物激活和破坏潜伏的HIV病毒的潜力。8名经过抗逆转录病毒疗法后处于医学上稳定的HIV病人服用伏立诺他，然后测试他们体内活跃的HIV病毒水平，并且与服用这种药物之前的水平进行比较。

研究人员发现这些接受伏立诺他治疗的病人体内CD4+ T细胞中HIV病毒RNA水平平均增加4.5倍，从而证实HIV病毒被脱去伪装，从潜伏状态暴露出来。这是第一次已发布的研究证实去乙酰化酶抑制剂有潜力破除潜伏病毒库中的潜伏性。这项研究提供令人信服的证据表明人们可能采用一种新策略来直接攻击和根除潜伏的HIV病毒感染。

破除HIV病毒的潜伏性只是治愈HIV病毒感染的第一步，但其为我们带来了彻底治愈艾滋病的曙光。

转自http://www.bioon.com/biology/sars/526916.shtml （有删改）


Administration of vorinostat disrupts HIV-1 latency in patients on antiretroviral therapy

N. M. Archin, A. L. Liberty, A. D. Kashuba, S. K. Choudhary, J. D. Kuruc, A. M. Crooks, D. C. Parker, E. M. Anderson, M. F. Kearney, M. C. Strain, D. D. Richman, M. G. Hudgens, R. J. Bosch, J. M. Coffin, J. J. Eron, D. J. Hazuda, D. M. Margolis.

Despite antiretroviral therapy, proviral latency of human immunodeficiency virus type 1 (HIV-1) remains a principal obstacle to curing the infection1. Inducing the expression of latent genomes within resting CD4+ T cells is the primary strategy to clear this reservoir2, 3. Although histone deacetylase inhibitors such as suberoylanilide hydroxamic acid (also known as vorinostat, VOR) can disrupt HIV-1 latency in vitro4, 5, 6, the utility of this approach has never been directly proven in a translational clinical study of HIV-infected patients. Here we isolated the circulating resting CD4+ T cells of patients in whom viraemia was fully suppressed by antiretroviral therapy, and directly studied the effect of VOR on this latent reservoir. In each of eight patients, a single dose of VOR increased both biomarkers of cellular acetylation, and simultaneously induced an increase in HIV RNA expression in resting CD4+ cells (mean increase, 4.8-fold). This demonstrates that a molecular mechanism known to enforce HIV latency can be therapeutically targeted in humans, provides proof-of-concept for histone deacetylase inhibitors as a therapeutic class, and defines a precise approach to test novel strategies to attack and eradicate latent HIV infection directly.

原文链接http://www.nature.com/nature/jou ... 86.html#/affil-auth

marine0425030

发表于 2012-8-21 09:31 marine0425030
介绍一片博文给大家

http://tagbasicscienceproject.typepad.com/tags_basic_science_vaccin/2012/07/hopes-raised-by-hdac-inhibitor-but-uncertainties-remain.html

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