Reactivation of latent HIV-1 by new semi-synthetic ingenol esters.
Reactivation of latent HIV-1 by new semi-synthetic ingenol esters.
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DOI：
10.1016/j.virol.2014.05.033
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发表时间：
2014-08
期刊：
影响因子：
3.7
通讯作者：
Aguiar, Renato Santana
中科院分区：
文献类型：
--
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
HIV建立长期潜伏感染的能力主要是由于静息记忆T淋巴细胞中病毒基因组的转录沉默。在这里，我们表明，新的半合成巨大戟二萜醇酯重新激活潜伏的艾滋病毒水库。在所测试的化合物中，3-己酰基-巨大戟二萜醇（ING B）比已知的激活剂如SAHA、巨大戟二萜醇3，20-二苯甲酸酯、TNF-α、PMA和HMBA更有效地再激活潜伏的HIV。ING B激活PKC亚型，随后NF-κB核转位。由于病毒的再活化依赖于LTR启动子区ING B中完整的NF-κB结合位点，我们已经证明。ING B能够在原代HIV感染的静息细胞中重新激活病毒转录高达12倍，与SAHA组合高达25倍。此外，ING B促进P-TEF B亚基CDK 9/Cyclin T1的上调。ING B在促进转录起始和延伸方面的作用使该化合物成为与抑制性HAART组合的抗HIV潜伏药物的强有力候选物。
The ability of HIV to establish long-lived latent infection is mainly due to transcriptional silencing of viral genome in resting memory T lymphocytes. Here, we show that new semi-synthetic ingenol esters reactivate latent HIV reservoirs. Amongst the tested compounds, 3-caproyl-ingenol (ING B) was more potent in reactivating latent HIV than known activators such as SAHA, ingenol 3,20-dibenzoate, TNF-α, PMA and HMBA. ING B activated PKC isoforms followed by NF-κB nuclear translocation. As virus reactivation is dependent on intact NF-κB binding sites in the LTR promoter region ING B, we have shown that. ING B was able to reactivate virus transcription in primary HIV-infected resting cells up to 12 fold and up to 25 fold in combination with SAHA. Additionally, ING B promoted up-regulation of P-TEFb subunits CDK9/Cyclin T1. The role of ING B on promoting both transcription initiation and elongation makes this compound a strong candidate for an anti-HIV latency drug combined with suppressive HAART.
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影响因子：
4.2
作者：
Ersvaer E;Kittang AO;Hampson P;Sand K;Gjertsen BT;Lord JM;Bruserud O
通讯作者：
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影响因子：
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