Department of Medicine, University of California at San Diego.
VA San Diego Healthcare System and Veterans Medical Research Foundation, San Diego, California, USA.
Curr Opin HIV AIDS. 2024 Mar 1;19(2):47-55. doi: 10.1097/COH.0000000000000838. Epub 2023 Dec 20.
Expression of noncoding RNAs (ncRNAs) is more tissue and cell type-specific than expression of protein-coding genes. Understanding the mechanisms of action of ncRNAs and their roles in HIV replication and latency may inform targets for the latent HIV reservoir reactivation or elimination with high specificity to CD4 + T cells latently infected with HIV.
While the number of studies in the field of ncRNAs and HIV is limited, evidence points to complex interactions between different ncRNAs, protein-coding RNAs, and proteins. Latency-reversing agents modulate the expression of ncRNAs, with some effects being inhibitory for HIV reactivation. An important limitation of basic research on the ncRNA mechanisms of action is the reliance on cell lines. Because of cell type specificity, it is uncertain whether the ncRNAs function similarly in primary cells.
Comprehensive functional screens to uncover all ncRNAs that regulate HIV expression and the detailed exploration of their mechanisms of action in relevant cell types are needed to identify promising targets for HIV reservoir clearance. Classes of ncRNAs as a whole rather than individual ncRNAs might represent an attractive target for reservoir elimination. Compound screens for latency reversal should factor in the complexity of their effects on ncRNAs.
综述目的：非编码 RNA（ncRNA）的表达比蛋白质编码基因的表达更具有组织和细胞类型特异性。了解 ncRNA 的作用机制及其在 HIV 复制和潜伏中的作用，可能为潜伏 HIV 库的激活或消除提供目标，具有针对 HIV 潜伏感染 CD4+T 细胞的高度特异性。
最新发现：尽管 ncRNA 和 HIV 领域的研究数量有限，但有证据表明不同的 ncRNA、编码 RNA 和蛋白质之间存在复杂的相互作用。潜伏逆转剂调节 ncRNA 的表达，其中一些作用对 HIV 激活具有抑制作用。ncRNA 作用机制的基础研究的一个重要限制是依赖细胞系。由于细胞类型特异性，尚不确定 ncRNA 是否在原代细胞中发挥类似作用。
总结：需要进行全面的功能筛选，以揭示所有调节 HIV 表达的 ncRNA，并在相关细胞类型中详细探索其作用机制，以确定有希望清除 HIV 储存库的靶标。ncRNA 作为一个整体类别而非单个 ncRNA 可能代表消除储存库的有吸引力的目标。潜伏逆转的化合物筛选应考虑其对 ncRNA 的复杂影响。
