Boliar Saikat, Russell David G
Microbiology and Immunology, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853, USA.
Mol Ther Nucleic Acids. 2021 Feb 10;23:1272-1280. doi: 10.1016/j.omtn.2021.02.004. eCollection 2021 Mar 5.
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.
大约25年前抗逆转录病毒疗法的出现，已将HIV-1感染转变为一种可控的慢性病，尽管仍然无法治愈。治疗方案无法清除那些以表观遗传沉默状态隐匿病毒的潜伏感染细胞，这构成了一个主要障碍。当前的治愈方法集中在“激活并清除”策略上，该策略使用潜伏逆转剂来化学性逆转潜伏感染细胞中前病毒的静止状态，随后通过免疫介导清除重新激活的细胞。迄今为止，已有数百种化合物被研究用于病毒激活，但尚无一种能实现功能性治愈。仅这些潜伏逆转剂（LRA）的不足表明迫切需要其他替代方法，如基因操作。长链非编码RNA（lncRNA）是一类新兴的调节性RNA，在包括表观遗传调控在内的许多细胞过程中发挥功能作用。一些lncRNA已被证明在HIV-
