Fighting HIV-1 Persistence: At the Crossroads of "Shoc-K and B-Lock".
Fighting HIV-1 Persistence: At the Crossroads of "Shoc-K and B-Lock".
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DOI：
10.3390/pathogens10111517
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发表时间：
2021-11-20
期刊：
影响因子：
--
通讯作者：
Sgarbanti M
中科院分区：
文献类型：
--
作者：
Acchioni C;Palermo E;Sandini S;Acchioni M;Hiscott J;Sgarbanti M
尽管高效抗逆转录病毒疗法（HAART）取得了成功，但整合的HIV-1前病毒DNA无法从受感染个体中根除。HAART疗法不能消灭免疫系统不可见的潜伏感染细胞。特定组织和免疫特权部位的病毒庇护所可能导致残留的病毒复制，从而导致HIV-1的持续存在。“Shock or Kick and Kill”方法在HAART存在的情况下使用潜伏期逆转剂（LRAs），然后由于病毒细胞病变效应和免疫介导的清除而杀死细胞。在不同的CD4+ T细胞库中，HIV-1的体内再激活可能需要不同的LRAs，从而激活作用于整合的前病毒HIV-1 LTR的细胞转录因子。LRA药物的一个重要要求是在不引起全身免疫激活的情况下重新激活病毒转录和复制。toll样受体、RIG-I样受体和STING激动剂最近作为一类新的LRAs出现，它们可以增强再激活T淋巴细胞的选择性凋亡。挑战在于将体外观察扩展到HIV-1阳性患者。还需要进一步的研究来克服保护潜伏感染细胞不被免疫系统重新激活和/或消除的机制。阻断和锁定替代策略旨在使用潜伏期促进/诱导剂（LPAs/LIAs）阻断潜伏前病毒重新激活转录的能力，以实现对潜在残留病毒复制的长期锁定。Shock and Kill和Block and Lock两种方法可能不仅是相互替代的，而且如果结合在一起（一个接一个），或者同时给出(即“Shock - k （Kill) and B(Block)-Lock”），它们可能代表一种更好的功能性治愈方法。
Despite the success of highly active antiretroviral therapy (HAART), integrated HIV-1 proviral DNA cannot be eradicated from an infected individual. HAART is not able to eliminate latently infected cells that remain invisible to the immune system. Viral sanctuaries in specific tissues and immune-privileged sites may cause residual viral replication that contributes to HIV-1 persistence. The “Shock or Kick, and Kill” approach uses latency reversing agents (LRAs) in the presence of HAART, followed by cell-killing due to viral cytopathic effects and immune-mediated clearance. Different LRAs may be required for the in vivo reactivation of HIV-1 in different CD4+ T cell reservoirs, leading to the activation of cellular transcription factors acting on the integrated proviral HIV-1 LTR. An important requirement for LRA drugs is the reactivation of viral transcription and replication without causing a generalized immune activation. Toll-like receptors, RIG-I like receptors, and STING agonists have emerged recently as a new class of LRAs that augment selective apoptosis in reactivated T lymphocytes. The challenge is to extend in vitro observations to HIV-1 positive patients. Further studies are also needed to overcome the mechanisms that protect latently infected cells from reactivation and/or elimination by the immune system. The Block and Lock alternative strategy aims at using latency promoting/inducing agents (LPAs/LIAs) to block the ability of latent proviruses to reactivate transcription in order to achieve a long term lock down of potential residual virus replication. The Shock and Kill and the Block and Lock approaches may not be only alternative to each other, but, if combined together (one after the other), or given all at once [namely “Shoc-K(kill) and B(block)-Lock”], they may represent a better approach to a functional cure.
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DOI：
10.1038/mtna.2015.31
发表时间：
2015-10-27
期刊：
Molecular therapy. Nucleic acids
影响因子：
--
作者：
Ahlenstiel C;Mendez C;Lim ST;Marks K;Turville S;Cooper DA;Kelleher AD;Suzuki K
通讯作者：
Suzuki K
影响因子：
64.8
作者：
Borducchi, Erica N.;Cabral, Crystal;Stephenson, Kathryn E.;Liu, Jinyan;Abbink, Peter;Ng'ang'a, David;Nkolola, Joseph P.;Brinkman, Amanda L.;Peter, Lauren;Lee, Benjamin C.;Jimenez, Jessica;Jetton, David;Mondesir, Jade;Mojta, Shanell;Chandrashekar, Abishek;Molloy, Katherine;Alter, Galit;Gerold, Jeffrey M.;Hill, Alison L.;Lewis, Mark G.;Pau, Maria G.;Schuitemaker, Hanneke;Hesselgesser, Joseph;Geleziunas, Romas;Kim, Jerome H.;Robb, Merlin L.;Michael, Nelson L.;Barouch, Dan H.
通讯作者：
Barouch, Dan H.
影响因子：
5.4
作者：
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通讯作者：
Marconi, Vincent
影响因子：
6.4
作者：
Archin, Nancy M.;Bateson, Rosalie;Margolis, David M.
通讯作者：
Margolis, David M.
影响因子：
20.3
作者：
Bosque, Alberto;Planelles, Vicente
通讯作者：
Planelles, Vicente