Lnc(ing)RNAs to the "shock and kill" strategy for HIV-1 cure.

Lnc(ing)RNAs to the "shock and kill" strategy for HIV-1 cure.
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DOI:
10.1016/j.omtn.2021.02.004
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发表时间:
2021-03-05
期刊:
Molecular therapy. Nucleic acids
影响因子:
--
通讯作者:
Russell DG
Russell DG
中科院分区:
其他
文献类型:
--
作者:
Boliar S;Russell DG

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近25年前,抗逆转录病毒疗法的出现将HIV-1感染转变为一种可控制的慢性疾病,尽管仍然无法治愈。治疗方案无法消除潜伏感染的细胞,这些细胞使病毒处于表观遗传沉默状态,这构成了一个主要障碍。目前的治疗方法集中在“休克和杀伤”策略上,该策略使用潜伏逆转剂在化学上逆转潜伏感染细胞中的前病毒静止,然后免疫介导清除重新激活的细胞。到目前为止,已经研究了数百种化合物用于病毒再激活,但没有一种化合物能产生功能性治愈。这些延迟逆转剂(LRAs)本身的不足表明迫切需要额外的替代方法,如基因操作。长链非编码rna (lncRNAs)是一类新兴的调控rna,在许多细胞过程中发挥功能作用,包括表观遗传调节。许多lncrna已经被认为在HIV-1潜伏期中发挥重要作用,因此,lncrna的药理学调节构成了HIV-1治愈研究的合理替代方法。在这篇综述中,我们讨论了lncrna在HIV-1感染中的作用的知识现状,并探讨了lncrna介导的遗传方法在HIV-1治疗的休克和杀伤策略中的范围。在生物医学研究中,治愈HIV-1仍然是一个艰巨的挑战。最近的证据表明lncrna在HIV-1感染中起关键作用。本文综述了lncRNAs在HIV-1潜伏期中的作用,并探讨了lncRNAs作为HIV-1治愈治疗靶点的潜力。
The advent of antiretroviral therapy almost 25 years ago has transformed HIV-1 infection into a manageable chronic condition, albeit still incurable. The inability of the treatment regimen to eliminate latently infected cells that harbor the virus in an epigenetically silent state poses a major hurdle. Current cure approaches are focused on a “shock and kill” strategy that uses latency-reversing agents to chemically reverse the proviral quiescence in latently infected cells, followed by immune-mediated clearance of reactivated cells. To date, hundreds of compounds have been investigated for viral reactivation, yet none has resulted in a functional cure. The insufficiency of these latency-reversing agents (LRAs) alone indicates a critical need for additional, alternate approaches such as genetic manipulation. Long non-coding RNAs (lncRNAs) are an emerging class of regulatory RNAs with functional roles in many cellular processes, including epigenetic modulation. A number of lncRNAs have already been implicated to play important roles in HIV-1 latency and, as such, pharmacological modulation of lncRNAs constitutes a rational alternative approach in HIV-1 cure research. In this review, we discuss the current state of knowledge of the role of lncRNAs in HIV-1 infection and explore the scope for a lncRNA-mediated genetic approach within the shock and kill strategy of HIV-1 cure. A cure for HIV-1 remains a formidable challenge in biomedical research. Recent evidence indicates critical roles for lncRNAs in HIV-1 infection. This review summarizes the current knowledge of the roles of lncRNAs in HIV-1 latency and explores the potential of lncRNAs as therapeutic targets for an HIV-1 cure.
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