Picomolar dichotomous activity of gnidimacrin against HIV-1.
Picomolar dichotomous activity of gnidimacrin against HIV-1.
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DOI：
10.1371/journal.pone.0026677
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Chen CH
中科院分区：
文献类型：
--
作者：
Huang L;Ho P;Yu J;Zhu L;Lee KH;Chen CH
高效抗逆转录病毒疗法（HAART）为控制HIV-1在感染个体中的复制提供了一种有希望的方法。然而，使用hart， HIV-1被抑制而不是根除，因为HIV-1在潜伏病毒库中持续存在。因此，清除潜伏宿主中的病毒是根除HIV-1感染的重要策略。在这项研究中，我们发现先前报道的具有强效抗癌细胞活性的daphnane二萜gnidimacrin可以激活HIV-1复制，并在皮摩尔浓度下杀死持续感染的细胞。除了从潜伏感染细胞中清除HIV-1的潜力外，gnidimacrin在平均浓度低于10 pM时有效抑制外周血单核细胞（PBMCs）的HIV-1 R5病毒感染。相比之下，gnidimacrin仅部分抑制pbmc的HIV-1 ×4病毒感染。gnidimacrin较强的抗HIV-1 R5病毒活性与其下调HIV-1副受体CCR5的作用有关。gnidimacrin的抗r5病毒活性被一种选择性蛋白激酶C β抑制剂enzastaurin完全消除，这表明蛋白激酶C β在PBMCs中gnidimacrin的抗hiv -1活性中起关键作用。综上所述，这些结果表明，gnidimacrin可以激活潜伏的HIV-1，特异性杀死HIV-1持续感染的细胞，并在皮摩尔浓度下抑制R5病毒。
Highly active antiretroviral therapy (HAART) has offered a promising approach for controlling HIV-1 replication in infected individuals. However, with HARRT, HIV-1 is suppressed rather than eradicated due to persistence of HIV-1 in latent viral reservoirs. Thus, purging the virus from latent reservoirs is an important strategy toward eradicating HIV-1 infection. In this study, we discovered that the daphnane diterpene gnidimacrin, which was previously reported to have potent anti-cancer cell activity, activated HIV-1 replication and killed persistently-infected cells at picomolar concentrations. In addition to its potential to purge HIV-1 from latently infected cells, gnidimacrin potently inhibited a panel of HIV-1 R5 virus infection of peripheral blood mononuclear cells (PBMCs) at an average concentration lower than 10 pM. In contrast, gnidimacrin only partially inhibited HIV-1 ×4 virus infection of PBMCs. The strong anti-HIV-1 R5 virus activity of gnidimacrin was correlated with its effect on down-regulation of the HIV-1 coreceptor CCR5. The anti-R5 virus activity of gnidimacrin was completely abrogated by a selective protein kinase C beta inhibitor enzastaurin, which suggests that protein kinase C beta plays a key role in the potent anti-HIV-1 activity of gnidimacrin in PBMCs. In summary, these results suggest that gnidimacrin could activate latent HIV-1, specifically kill HIV-1 persistently infected cells, and inhibit R5 viruses at picomolar concentrations.
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影响因子：
56.9
作者：
FOLKS, TM;JUSTEMENT, J;FAUCI, AS
通讯作者：
FAUCI, AS
DOI：
10.1073/pnas.86.7.2365
发表时间：
1989-04-01
影响因子：
11.1
作者：
FOLKS, TM;CLOUSE, KA;FAUCI, AS
通讯作者：
FAUCI, AS
影响因子：
6.4
作者：
Yoshida, M;Heike, Y;Wakasugi, H
通讯作者：
Wakasugi, H
影响因子：
56.9
作者：
Wender, Paul A.;Kee, Jung-Min;Warrington, Jeffrey M.
通讯作者：
Warrington, Jeffrey M.
影响因子：
5.2
作者：
Asada, Yoshihisa;Sukemori, Aya;Watanabe, Takashi;Malla, Kuber J.;Yoshikawa, Takafumi;Li, Wei;Koike, Kazuo;Chen, Chin-Ho;Akiyama, Toshiyuki;Qian, Keduo;Nakagawa-Goto, Kyoko;Morris-Natschke, Susan L.;Lee, Kuo-Hsiung
通讯作者：
Lee, Kuo-Hsiung