Department of Infectious Diseases, Zhongnan Hospital of Wuhan University, No. 169, Donghu Road, Wuchang District, Wuhan, 430071, Hubei Province, China.
State Key Laboratory of Virology, Modern Virology Research Center, College of Life Sciences, Wuhan University, Wuhan, 430071, Hubei Province, China.
Sci Rep. 2023 Dec 15;13(1):22493. doi: 10.1038/s41598-023-49595-z.
Long noncoding RNAs (lncRNAs) play important roles in regulating HIV-1 infection and virus-host interactions. However, it is unclear whether and how ART alters lncRNAs in HIV-infected patients. In the present study, we investigated changes of lncRNAs in PBMCs from HIV-1 patients pre- and post-ART. We identified a total of 974 lncRNAs whose expression was restored to normal levels after ART. Cis-acting analysis showed that six lncRNAs have cis-regulated target genes, among which RP11-290F5.1 and interferon regulatory factor 2 (IRF2) were reported to promote HIV replication. Furthermore, we found that lncRNA CTB-119C2.1, which regulates most mRNAs with differential expression in PBMCs from HIV-1 infected patients after ART, was significantly upregulated by RNA-seq and qRT-PCR assays. KEGG analysis of CTB-119C2.1-associated genes revealed that most of the genes are involved in the p53 signaling pathway and pathways related to cell cycle and DNA replication. Our findings thus reveal the dynamic change of lncRNAs in people living with HIV-1 pre- and post-ART and warrant further investigation of the role of lncRNAs in HIV-1 pathogenesis and treatment.
长链非编码 RNA(lncRNAs)在调节 HIV-1 感染和病毒-宿主相互作用方面发挥着重要作用。然而,目前尚不清楚抗逆转录病毒治疗(ART)是否以及如何改变 HIV 感染患者的 lncRNAs。在本研究中,我们研究了 HIV-1 患者接受 ART 前后 PBMCs 中 lncRNAs 的变化。我们总共鉴定了 974 个 lncRNAs,其表达在 ART 后恢复到正常水平。顺式作用分析表明,有 6 个 lncRNAs 具有顺式调控的靶基因,其中 RP11-290F5.1 和干扰素调节因子 2(IRF2)被报道可促进 HIV 复制。此外,我们发现 lncRNA CTB-119C2.1,它调节了 HIV-1 感染患者 PBMCs 中经过 ART 治疗后差异表达的大多数 mRNAs,在 RNA-seq 和 qRT-PCR 分析中显著上调。CTB-119C2.1 相关基因的 KEGG 分析表明,大多数基因参与 p53 信号通路以及与细胞周期和 DNA 复制相关的途径。因此,我们的研究结果揭示了 HIV-1 患者接受 ART 前后 lncRNAs 的动态变化,并需要进一步研究 lncRNAs 在 HIV-1 发病机制和治疗中的作用。