Molecular control of HIV-1 postintegration latency: implications for the development of new therapeutic strategies.
Molecular control of HIV-1 postintegration latency: implications for the development of new therapeutic strategies.
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DOI：
10.1186/1742-4690-6-111
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发表时间：
2009-12-04
期刊：
影响因子：
3.3
通讯作者：
Van Lint C
中科院分区：
文献类型：
--
作者：
Colin L;Van Lint C
在接受高效抗逆转录病毒治疗（HAART）的感染患者中，HIV - 1潜伏储存库的持续存在是根除病毒的主要障碍，因为中断治疗不可避免地会导致血浆病毒血症反弹。感染后早期就会建立潜伏状态，尤其（但不限于）在静息记忆CD4 + T细胞中，并且涉及众多宿主和病毒反式作用蛋白，以及转录干扰、RNA沉默、表观遗传修饰和染色质组织等过程。为了消除潜伏储存库，人们设想了新的策略，包括在潜伏感染细胞中重新激活HIV - 1转录，同时维持HAART以防止新的感染。困难在于，理论上单个残留的潜伏感染细胞就可以重新引发感染。在此，我们综述了我们目前对HIV - 1潜伏建立和维持以及从潜伏状态转录再激活所涉及的分子机制的理解。我们强调了基于对潜伏的这种理解的新治疗策略的潜力。同时使用多种化合物的组合能够在多个层面靶向转录抑制，并可促进从潜伏状态的逃逸和病毒储存库的清除。我们描述了免疫T细胞激活剂、NF - κB信号通路诱导剂以及去乙酰化酶和组蛋白及DNA甲基转移酶抑制剂单独使用或组合使用时当前的优势和局限性。虽然明天不会有解决方案，但对抗HIV - 1潜伏储存库的战斗正在顺利进行。
The persistence of HIV-1 latent reservoirs represents a major barrier to virus eradication in infected patients under HAART since interruption of the treatment inevitably leads to a rebound of plasma viremia. Latency establishes early after infection notably (but not only) in resting memory CD4+ T cells and involves numerous host and viral trans-acting proteins, as well as processes such as transcriptional interference, RNA silencing, epigenetic modifications and chromatin organization. In order to eliminate latent reservoirs, new strategies are envisaged and consist of reactivating HIV-1 transcription in latently-infected cells, while maintaining HAART in order to prevent de novo infection. The difficulty lies in the fact that a single residual latently-infected cell can in theory rekindle the infection. Here, we review our current understanding of the molecular mechanisms involved in the establishment and maintenance of HIV-1 latency and in the transcriptional reactivation from latency. We highlight the potential of new therapeutic strategies based on this understanding of latency. Combinations of various compounds used simultaneously allow for the targeting of transcriptional repression at multiple levels and can facilitate the escape from latency and the clearance of viral reservoirs. We describe the current advantages and limitations of immune T-cell activators, inducers of the NF-κB signaling pathway, and inhibitors of deacetylases and histone- and DNA- methyltransferases, used alone or in combinations. While a solution will not be achieved by tomorrow, the battle against HIV-1 latent reservoirs is well- underway.
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影响因子：
3.3
作者：
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