Suzuki Kazuo, Ahlenstiel Chantelle, Marks Katherine, Kelleher Anthony D
1] Immunovirology laboratory, St Vincent's Centre for Applied Medical Research, Darlinghurst, Australia [2] The Kirby Institute, University of New South Wales, Sydney, Australia.
The Kirby Institute, University of New South Wales, Sydney, Australia.
Mol Ther Nucleic Acids. 2015 Jan 27;4(1):e222. doi: 10.1038/mtna.2014.67.
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.
尽管联合抗逆转录病毒疗法（cART）进行了长期且强化的治疗，能有效抑制血浆病毒血症，但HIV-1的整合前病毒仍以潜伏感染的形式存在于静息记忆CD4(+) T细胞中。cART治疗并不能显著降低潜伏感染的负担。一旦停止cART治疗，绝大多数患者体内的HIV-1会从这些病毒库中重新开始复制。越来越多的证据支持非编码RNA（ncRNA），包括微小RNA（miRNA）、反义（as）RNA和短干扰（si）RNA在HIV-1转录调控中发挥作用。这似乎是通过与HIV-1启动子区域相互作用介导的。病毒miRNA有可能作为HIV转录的正调控或负调控因子。此外，抑制病毒编码的长asRNA可诱导正转录调控，而靶向NF-κB区域的siRNA反义链可抑制病毒转录。深入了解ncRNA与HIV-1 U3启动子区域之间的相互作用可能会带来控制HIV病毒库的新方法。本综述聚焦于与启动子相关的ncRNA，特别强调它们在决定HIV-1建立活跃感染还是潜伏感染中所起的作用。
