HIV Latency-Reversing Agents Have Diverse Effects on Natural Killer Cell Function.
HIV Latency-Reversing Agents Have Diverse Effects on Natural Killer Cell Function.
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DOI：
10.3389/fimmu.2016.00356
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发表时间：
2016
影响因子：
7.3
通讯作者：
Margolis DM
中科院分区：
文献类型：
--
作者：
Garrido C;Spivak AM;Soriano-Sarabia N;Checkley MA;Barker E;Karn J;Planelles V;Margolis DM
为了清除持续的HIV感染并实现HIV疾病的持久无治疗缓解，正在进行广泛的临床前研究和早期试点临床试验，以开发和测试可以逆转潜伏的HIV感染并将病毒抗原呈递给免疫系统以进行清除的药物。因此，了解潜伏期逆转剂（LRA）对清除感染细胞所需的免疫效应器功能的影响至关重要。我们评估了LRA对天然杀伤（NK）细胞功能的影响，NK细胞是先天免疫系统的主要效应细胞。我们研究了三种组蛋白脱乙酰酶抑制剂[SAHA或伏立诺他（VOR）、罗米地辛和帕比司他（PNB）]和两种蛋白激酶C激动剂[prostratin（PROST）和巨大戟二萜醇]对原代NK细胞的抗病毒活性、细胞毒性、细胞因子分泌、表型和活力的影响。我们发现离体暴露于VOR对所有评估参数的影响最小，而PNB导致NK细胞活力、抗病毒活性和细胞毒性降低。PROST引起非特异性NK细胞活化，有趣的是，提高了抗病毒活性。总的来说，我们发现LRA可以改变NK细胞的功能和命运，在制定清除持续性HIV感染的策略时必须仔细考虑这些影响。
In an effort to clear persistent HIV infection and achieve a durable therapy-free remission of HIV disease, extensive pre-clinical studies and early pilot clinical trials are underway to develop and test agents that can reverse latent HIV infection and present viral antigen to the immune system for clearance. It is, therefore, critical to understand the impact of latency-reversing agents (LRAs) on the function of immune effectors needed to clear infected cells. We assessed the impact of LRAs on the function of natural killer (NK) cells, the main effector cells of the innate immune system. We studied the effects of three histone deacetylase inhibitors [SAHA or vorinostat (VOR), romidepsin, and panobinostat (PNB)] and two protein kinase C agonists [prostratin (PROST) and ingenol] on the antiviral activity, cytotoxicity, cytokine secretion, phenotype, and viability of primary NK cells. We found that ex vivo exposure to VOR had minimal impact on all parameters assessed, while PNB caused a decrease in NK cell viability, antiviral activity, and cytotoxicity. PROST caused non-specific NK cell activation and, interestingly, improved antiviral activity. Overall, we found that LRAs can alter the function and fate of NK cells, and these effects must be carefully considered as strategies are developed to clear persistent HIV infection.
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影响因子：
--
作者：
McManamy, Mary E. Manson;Hakre, Shweta;Margolis, David M.
通讯作者：
Margolis, David M.
影响因子：
3.7
作者：
Jose, Diego Pandelo;Bartholomeeusen, Koen;da Cunha, Rodrigo Delvecchio;Abreu, Celina Monteiro;Glinski, Jan;Ferreira da Costa, Thais Barbizan;Mello Bacchi Rabay, Ana Flavia;Pianowski Filho, Luiz Francisco;Dudycz, Lech W.;Ranga, Udaykumar;Peterlin, Boris Matija;Pianowski, Luiz Francisco;Tanuri, Amilcar;Aguiar, Renato Santana
通讯作者：
Aguiar, Renato Santana
影响因子：
20.3
作者：
Fiegler, Nathalie;Textor, Sonja;Cerwenka, Adelheid
通讯作者：
Cerwenka, Adelheid
影响因子：
5.5
作者：
Cummings, Jean-Saville;Moreno-Nieves, Uriel Y.;Scott-Algara, Daniel
通讯作者：
Scott-Algara, Daniel
影响因子：
5.4
作者：
Olesen, Rikke;Vigano, Selena;Lichterfeld, Mathias
通讯作者：
Lichterfeld, Mathias