Targeting the Brain Reservoirs: Toward an HIV Cure.
Targeting the Brain Reservoirs: Toward an HIV Cure.
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DOI：
10.3389/fimmu.2016.00397
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发表时间：
2016
影响因子：
7.3
通讯作者：
Schwartz C
中科院分区：
文献类型：
--
作者：
Marban C;Forouzanfar F;Ait-Ammar A;Fahmi F;El Mekdad H;Daouad F;Rohr O;Schwartz C
国际艾滋病协会在“走向艾滋病毒治愈”行动中的最高研究优先事项之一是清除或减少所有潜伏感染细胞的库。这种策略是基于潜在的水库（休克），然后加强联合抗逆转录病毒疗法（cART）杀死他们（杀死）的重新激活。中枢神经系统（CNS）具有潜在的潜伏感染细胞，即，血管周围的巨噬细胞、小胶质细胞和星形胶质细胞需要被清除。然而，中枢神经系统有几个特点，可能会妨碍实现治愈。在这篇综述中，我们讨论了几个局限性，以消除脑水库，我们如何可以绕过这些限制，使其努力在四个方向：（i）设计有效的潜伏期逆转剂的CNS细胞类型，（ii）改善cART靶向HIV转录，（iii）改善交付的HIV药物在CNS和CNS细胞类型，和（iv）开发治疗性免疫。作为这些努力的先决条件，我们还认为，更好地理解参与建立和持久的HIV潜伏期在大脑水库的分子机制是必不可少的，以设计新的分子的战略，旨在实现治愈，例如“休克和杀死”的战略。
One of the top research priorities of the international AIDS society by the action “Towards an HIV Cure” is the purge or the decrease of the pool of all latently infected cells. This strategy is based on reactivation of latently reservoirs (the shock) followed by an intensifying combination antiretroviral therapy (cART) to kill them (the kill). The central nervous system (CNS) has potential latently infected cells, i.e., perivascular macrophages, microglial cells, and astrocytes that will need to be eliminated. However, the CNS has several characteristics that may preclude the achievement of a cure. In this review, we discuss several limitations to the eradication of brain reservoirs and how we could circumvent these limitations by making it efforts in four directions: (i) designing efficient latency-reversal agents for CNS-cell types, (ii) improving cART by targeting HIV transcription, (iii) improving delivery of HIV drugs in the CNS and in the CNS-cell types, and (iv) developing therapeutic immunization. As a prerequisite to these efforts, we also believe that a better comprehension of molecular mechanisms involved in establishment and persistence of HIV latency in brain reservoirs are essential to design new molecules for strategies aiming to achieve a cure for instance the “shock and kill” strategy.
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影响因子：
5.8
作者：
Chauhan A
通讯作者：
Chauhan A
影响因子：
8
作者：
Cherrier, T.;Suzanne, S.;Redel, L.;Calao, M.;Marban, C.;Samah, B.;Mukerjee, R.;Schwartz, C.;Gras, G.;Sawaya, B. E.;Zeichner, S. L.;Aunis, D.;Van Lint, C.;Rohr, O.
通讯作者：
Rohr, O.
影响因子：
11.1
作者：
Bouchat S;Delacourt N;Kula A;Darcis G;Van Driessche B;Corazza F;Gatot JS;Melard A;Vanhulle C;Kabeya K;Pardons M;Avettand-Fenoel V;Clumeck N;De Wit S;Rohr O;Rouzioux C;Van Lint C
通讯作者：
Van Lint C
影响因子：
4.6
作者：
Arrildt, Kathryn Twigg;Joseph, Sarah Beth;Swanstrom, Ronald
通讯作者：
Swanstrom, Ronald
影响因子：
7.5
作者：
Bres, Vanessa;Yoh, Sunnie M.;Jones, Katherine A.
通讯作者：
Jones, Katherine A.