PLos Pathgen:新南威尔士大学发现新方法让艾滋病病毒现形

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澳大利亚新南威尔士大学官网日前发布消息说，该校科学家参加的国际研究小组使用新方法，让艾滋病病毒现形。艾滋病至今没有找到根治的办法，原因之一是艾滋病病毒在人体内隐藏很深。艾滋病病毒能够与人体DNA结合，长时间在DNA中以休眠状态潜伏，借此躲避人体免疫系统和治疗药物的攻击。

一旦时机成熟，比如强化治疗暂停，隐藏的病毒就迅速活跃，并导致患者的症状重新出现。

此前，科学家已经发现，艾滋病毒实现潜伏得益于人体内的“组蛋白去乙酰化酶（HDAC）”蛋白酶，这种蛋白酶对染色体的结构修饰和基因表达调控起到重要作用。因此，从理论上可以推测，“HDAC抑制剂”有可能干扰艾滋病毒的潜伏，使其显形。

此次研究中，澳大利亚新南威尔士大学的克斯滕·凯尔奇（Kersten Koelsch）参与的国际研究小组使用一种抗肿瘤药“罗米地辛”进行测试。实验中，科学家们共选择了六名接受“抗逆转录病毒治疗”十年左右的艾滋病患者，平均年龄56岁。实验过程中，这些患者连续三周每周注射一次“罗米地辛”。然后，持续跟踪观察这些患者的身体状况。

结果发现，隐藏在这些患者DNA中的艾滋病病毒确实现形了。有关研究论文已刊登在新一期《科学公共图书馆病原体》上。

凯尔奇说，下一步研究是将“罗米地辛”治疗与其他艾滋病干预治疗措施结合起来，观察传统方法对于现形病毒的治疗效果。

凯尔奇说，围绕此次的成果，仍有许多待解之谜，比如目前仍无法确定新方法挖出隐藏病毒的效率，有多少现形了，有多少还没被挖出来。

凯尔奇说，此次研究为未来进一步调查研究艾滋病治疗干预措施奠定了关键的基础。不过人类距离完全治愈艾滋病还十分遥远。在目前阶段，艾滋病患者仍必须坚持传统治疗方法。

来源：新华网

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The Depsipeptide Romidepsin Reverses HIV-1 Latency In Vivo

Ole S. Søgaard , Mette E. Graversen, Steffen Leth, Rikke Olesen, Christel R. Brinkmann, Sara K. Nissen, Anne Sofie Kjaer, Mariane H. Schleimann, Paul W. Denton, William J. Hey-Cunningham, Kersten K. Koelsch, Giuseppe Pantaleo, Kim Krogsgaard, Maja Sommerfelt, Remi Fromentin, Nicolas Chomont, Thomas A. Rasmussen, Lars Østergaard, Martin Tolstrup

Pharmacologically-induced activation of replication competent proviruses from latency in the presence of antiretroviral treatment (ART) has been proposed as a step towards curing HIV-1 infection. However, until now, approaches to reverse HIV-1 latency in humans have yielded mixed results. Here, we report a proof-of-concept phase Ib/IIa trial where 6 aviremic HIV-1 infected adults received intravenous 5 mg/m2 romidepsin (Celgene) once weekly for 3 weeks while maintaining ART. Lymphocyte histone H3 acetylation, a cellular measure of the pharmacodynamic response to romidepsin, increased rapidly (maximum fold range: 3.7–7.7 relative to baseline) within the first hours following each romidepsin administration. Concurrently, HIV-1 transcription quantified as copies of cell-associated un-spliced HIV-1 RNA increased significantly from baseline during treatment (range of fold-increase: 2.4–5.0; p = 0.03). Plasma HIV-1 RNA increased from <20 copies/mL at baseline to readily quantifiable levels at multiple post-infusion time-points in 5 of 6 patients (range 46–103 copies/mL following the second infusion, p = 0.04). Importantly, romidepsin did not decrease the number of HIV-specific T cells or inhibit T cell cytokine production. Adverse events (all grade 1–2) were consistent with the known side effects of romidepsin. In conclusion, romidepsin safely induced HIV-1 transcription resulting in plasma HIV-1 RNA that was readily detected with standard commercial assays demonstrating that significant reversal of HIV-1 latency in vivo is possible without blunting T cell-mediated immune responses. These finding have major implications for future trials aiming to eradicate the HIV-1 reservoir.

http://journals.plos.org/plospat ... ournal.ppat.1005142