Promoter Targeting RNAs: Unexpected Contributors to the Control of HIV-1 Transcription.

Promoter Targeting RNAs: Unexpected Contributors to the Control of HIV-1 Transcription.
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DOI:
10.1038/mtna.2014.67
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发表时间:
2015-01-27
期刊:
Molecular therapy. Nucleic acids
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尽管使用联合抗逆转录病毒疗法(cART)进行长期和强化治疗,可有效抑制血浆病毒血症,但HIV-1的整合前病毒作为潜伏感染持续存在于静息记忆CD4 + T细胞中。用cART治疗并不能实质上减少潜伏感染的负担。一旦cART停止,绝大多数患者的HIV-1复制从这些储库复发。越来越多的证据支持非编码RNA(ncRNA),包括microRNA(miRNAs)、反义RNA(as)和短干扰RNA(si)在HIV-1转录调控中的作用。这似乎是通过与HIV-1启动子区域的相互作用介导的。病毒miRNAs具有作为HIV转录的正或负调节因子的潜力。此外,抑制病毒编码的long-asRNA可以诱导正性转录调控,而靶向NF-κ B区域的siRNA反义链抑制病毒转录。深入了解ncRNA和HIV-1 U3启动子区域之间的相互作用可能会导致控制HIV储库的新方法。本文综述了启动子相关的非编码RNA,特别强调了它们在决定HIV-1是否建立活动性或潜伏性感染中的作用。
In spite of prolonged and intensive treatment with combined antiretroviral therapy (cART), which efficiently suppresses plasma viremia, the integrated provirus of HIV-1 persists in resting memory CD4+ T cells as latent infection. Treatment with cART does not substantially reduce the burden of latent infection. Once cART is ceased, HIV-1 replication recrudesces from these reservoirs in the overwhelming majority of patients. There is increasing evidence supporting a role for noncoding RNAs (ncRNA), including microRNAs (miRNAs), antisense (as)RNAs, and short interfering (si)RNA in the regulation of HIV-1 transcription. This appears to be mediated by interaction with the HIV-1 promoter region. Viral miRNAs have the potential to act as positive or negative regulators of HIV transcription. Moreover, inhibition of virally encoded long-asRNA can induce positive transcriptional regulation, while antisense strands of siRNA targeting the NF-κB region suppress viral transcription. An in-depth understanding of the interaction between ncRNAs and the HIV-1 U3 promoter region may lead to new approaches for the control of HIV reservoirs. This review focuses on promoter associated ncRNAs, with particular emphasis on their role in determining whether HIV-1 establishes active or latent infection.
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