HIV Cure Research Center, Department of Internal Medicine and Pediatrics, Ghent University and Ghent University Hospital, 9000 Ghent, Belgium.
Int J Mol Sci. 2023 Jan 5;24(2):1031. doi: 10.3390/ijms24021031.
Lately, the interest in long non-coding RNAs (lncRNAs) as potential drug targets and predictive markers in the context of HIV-1 has peaked, but their in vivo expression and regulation remains largely unexplored. Therefore, the present study examined lncRNA expression patterns during a clinical antiretroviral treatment interruption (ATI) trial. Peripheral blood mononuclear cells were isolated from ten patients at four timepoints: prior to ATI, 7-15 days after stop, at viral rebound and 3 months post antiretroviral therapy re-initiation. RNA was extracted and RT-qPCR on five known HIV-1-related lncRNAs (HEAL, MALAT1, NEAT1, GAS5 and NRON) was performed and correlated with HIV-1 and host marker expression. All lncRNAs correlated stronger with interferon stimulated genes (ISGs) than with HIV-1 reservoir and replication markers. However, one lncRNA, HEAL, showed significant upregulation at viral rebound during ATI compared to baseline and re-initiation of therapy ( = 0.0010 and = 0.0094, respectively), following a similar viral-load-driven expression pattern to ISGs. In vitro knockdown of HEAL caused a significant reduction in HIV-1 infection levels, validating HEAL's importance for HIV-1 replication. We conclude that the HIV-1-promoting lncRNA HEAL is upregulated at viral rebound during ATI, most likely induced by viral cues.
最近，人们对长非编码 RNA（lncRNA）作为 HIV-1 潜在的药物靶点和预测标志物的兴趣达到了顶峰，但它们在体内的表达和调控仍在很大程度上未被探索。因此，本研究在一项临床抗逆转录病毒治疗中断（ATI）试验中检查了 lncRNA 的表达模式。从十位患者的四个时间点分离外周血单核细胞：ATI 前、停药后 7-15 天、病毒反弹时和重新开始抗逆转录病毒治疗后 3 个月。提取 RNA 并进行 RT-qPCR 检测五种已知的 HIV-1 相关 lncRNA（HEAL、MALAT1、NEAT1、GAS5 和 NRON），并与 HIV-1 和宿主标志物表达相关。所有 lncRNA 与干扰素刺激基因（ISGs）的相关性都强于与 HIV-1 储存库和复制标志物的相关性。然而，一种 lncRNA，HEAL，在 ATI 期间的病毒反弹时与基线和重新开始治疗相比（分别为 = 0.0010 和 = 0.0094）显著上调，与 ISGs 类似地遵循病毒负荷驱动的表达模式。HEAL 的体外敲低导致 HIV-1 感染水平显著降低，验证了 HEAL 对 HIV-1 复制的重要性。我们得出结论，HIV-1 促进的 lncRNA HEAL 在 ATI 期间的病毒反弹时上调，很可能是由病毒信号诱导的。
