Sulforaphane prevents the reactivation of HIV-1 by suppressing NFκB signaling.
Sulforaphane prevents the reactivation of HIV-1 by suppressing NFκB signaling.
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DOI：
10.1016/j.jve.2023.100341
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发表时间：
2023-09
影响因子：
5.5
通讯作者：
Singh VB
中科院分区：
文献类型：
--
作者：
Jamal I;Paudel A;Thompson L;Abdelmalek M;Khan IA;Singh VB
尽管联合抗逆转录病毒疗法（cART）已有20多年的历史，但彻底根除艾滋病毒仍然是一项艰巨的任务。虽然cART在限制新的感染周期和保持病毒载量低于可检测水平以及部分恢复免疫功能方面非常有效，但它不能提供治愈。显然，cART的中断导致病毒载量在几周内快速反弹。这些一致的观察结果表明，艾滋病毒能够作为一个不可检测的潜伏库在各种组织中持续存在，这些组织对抗逆转录病毒疗法仍然不敏感。驱动潜伏细胞进入深度潜伏期的“阻断和锁定”方法已成为实现功能性治愈的可行策略。它需要开发具有抗HIV功能的潜伏促进剂。最近的报道表明，萝卜硫素（SFN），诱导剂的NRF-2（核红细胞2相关因子2）介导的抗氧化信号，具有抗艾滋病毒的特性，限制艾滋病毒复制的早期阶段。然而，SFN对整合的前病毒表达的影响仍然没有被探索。我们假设SFN可能会促进延迟并阻止重新激活。我们的研究结果表明，SFN可以使潜伏感染的单核细胞和CD 4 + T细胞抵抗再活化。SFN治疗可拮抗已知的潜伏性激活剂、肿瘤坏死因子（TNF-α）和佛波醇12-肉豆蔻酸酯13-乙酸酯（PMA）的作用，并导致HIV转录、病毒RNA拷贝和p24水平显著降低。此外，发现这种再活化的阻断是由SFN诱导的NRF-2信号传导介导的，其特异性地降低NFκB信号传导的活化，从而限制HIV-1启动子（5′LTR）活性。总的来说，我们的研究提供了令人信服的证据，突出了SFN的潜伏期促进潜力，可用于“阻断和锁定”方法，以实现艾滋病毒治愈。
Despite more than 20 years of combination antiretroviral therapy (cART), complete eradication of HIV remains a daunting task. While cART has been very effective in limiting new cycles of infection and keeping viral load below detectable levels with partial restoration of immune functions, it cannot provide a cure. Evidently, the interruption of cART leads to a quick rebound of the viral load within a few weeks. These consistent observations have revealed HIV ability to persist as an undetectable latent reservoir in a variety of tissues that remain insensitive to antiretroviral therapies. The ‘Block-and-Lock’ approach to drive latent cells into deep latency has emerged as a viable strategy to achieve a functional cure. It entails the development of latency-promoting agents with anti-HIV functions. Recent reports have suggested sulforaphane (SFN), an inducer of NRF-2 (nuclear erythroid 2-related factor 2)-mediated antioxidative signaling, to possess anti-HIV properties by restricting HIV replication at the early stages. However, the effect of SFN on the expression of integrated provirus remains unexplored. We have hypothesized that SFN may promote latency and prevent reactivation. Our results indicate that SFN can render latently infected monocytes and CD4+ T cells resistant to reactivation. SFN treatments antagonized the effects of known latency reactivating agents, tumor necrosis pactor (TNF-α), and phorbol 12-myristate 13-acetate (PMA), and caused a significant reduction in HIV transcription, viral RNA copies, and p24 levels. Furthermore, this block of reactivation was found to be mediated by SFN-induced NRF-2 signaling that specifically decreased the activation of NFκB signaling and thus restricted the HIV-1 promoter (5′LTR) activity. Overall, our study provides compelling evidence to highlight the latency-promoting potential of SFN which could be used in the ‘Block-and-Lock’ approach to achieve an HIV cure.
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Tat 突变体有效抑制 HIV-1 复制。
影响因子：
3.7
作者：
Meredith LW;Sivakumaran H;Major L;Suhrbier A;Harrich D
通讯作者：
Harrich D
DOI：
10.1016/j.ddtec.2012.10.002
发表时间：
2013-12-01
期刊：
Drug discovery today. Technologies
影响因子：
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影响因子：
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作者：
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影响因子：
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作者：
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作者：
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