New Concepts in Therapeutic Manipulation of HIV-1 Transcription and Latency: Latency Reversal versus Latency Prevention.
New Concepts in Therapeutic Manipulation of HIV-1 Transcription and Latency: Latency Reversal versus Latency Prevention.
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DOI：
10.3390/v15081677
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发表时间：
2023-07-31
期刊：
影响因子：
--
通讯作者：
Browne EP
中科院分区：
文献类型：
--
作者：
Lewis CA;Margolis DM;Browne EP
抗逆转录病毒疗法（ART）已经大大改善了HIV-1感染者的预后，但治愈方法仍然难以捉摸。治愈的最大障碍是存在一个长期潜伏的水库，它存在于细胞类型和解剖区室的异质混合物中。消除潜伏库的努力主要集中在潜伏逆转策略上。然而，新的工作已经证明，大多数长期潜伏的水库是建立在ART启动的时间附近，这表明它可能是可能的配对干预与ART启动，以防止形成相当大的一部分的潜伏水库。随后的治疗与潜伏期逆转剂，结合免疫清除剂，可能是一个更容易处理的策略，完全清除潜伏水库的人新启动的ART。在这里，我们总结了潜伏期建立和维护的分子机制，正在努力开发有效的潜伏期逆转剂，和新的努力设计潜伏期预防剂。对潜伏期的建立和维持所涉及的分子机制的更好理解将有助于开发新的潜伏期预防和逆转方法，以最终根除潜伏性储库。
Antiretroviral therapy (ART) has dramatically improved the prognosis for people living with HIV-1, but a cure remains elusive. The largest barrier to a cure is the presence of a long-lived latent reservoir that persists within a heterogenous mix of cell types and anatomical compartments. Efforts to eradicate the latent reservoir have primarily focused on latency reversal strategies. However, new work has demonstrated that the majority of the long-lived latent reservoir is established near the time of ART initiation, suggesting that it may be possible to pair an intervention with ART initiation to prevent the formation of a sizable fraction of the latent reservoir. Subsequent treatment with latency reversal agents, in combination with immune clearance agents, may then be a more tractable strategy for fully clearing the latent reservoir in people newly initiating ART. Here, we summarize molecular mechanisms of latency establishment and maintenance, ongoing efforts to develop effective latency reversal agents, and newer efforts to design latency prevention agents. An improved understanding of the molecular mechanisms involved in both the establishment and maintenance of latency will aid in the development of new latency prevention and reversal approaches to ultimately eradicate the latent reservoir.
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影响因子：
6.7
作者：
Coffin JM;Bale MJ;Wells D;Guo S;Luke B;Zerbato JM;Sobolewski MD;Sia T;Shao W;Wu X;Maldarelli F;Kearney MF;Mellors JW;Hughes SH
通讯作者：
Hughes SH
影响因子：
56.9
作者：
BUKRINSKY, MI;STANWICK, TL;STEVENSON, M
通讯作者：
STEVENSON, M
DOI：
10.3390/v2102226
发表时间：
2010-10-01
期刊：
Viruses
影响因子：
--
作者：
D'Orso I;Frankel AD
通讯作者：
Frankel AD
影响因子：
5.4
作者：
Coull, JJ;Romerio, F;Margolis, DM
通讯作者：
Margolis, DM
DOI：
10.1073/pnas.94.24.13193
发表时间：
1997-11-25
影响因子：
11.1
作者：
Chun, TW;Stuyver, L;Fauci, AS
通讯作者：
Fauci, AS