Department of Veterinary and Biomedical Sciences, University of Minnesota, Saint Paul, MN 55108, USA.
Department of Mathematics, Statistics and Computer Science, Macalester College, Saint Paul, MN 55105, USA.
Viruses. 2022 Mar 25;14(4):683. doi: 10.3390/v14040683.
Since the onset of the HIV-1/AIDS epidemic in 1981, 75 million people have been infected with the virus, and the disease remains a public health crisis worldwide. Circular RNAs (circRNAs) are derived from excised exons and introns during backsplicing, a form of alternative splicing. The relevance of unconventional, non-capped, and non-poly(A) transcripts to transcriptomics studies remains to be routinely investigated. Knowledge gaps to be filled are the interface between host-encoded circRNAs and viral replication in chronically progressed patients and upon treatment with antiviral drugs. We implemented a bioinformatic pipeline and repurpose publicly archived RNA sequence reads from the blood of 19 HIV-1-positive patients that previously compared transcriptomes during viremia and viremia suppression by antiretroviral therapy (ART). The in silico analysis identified viremic patients' circRNA that became undetectable after ART. The circRNAs originated from a subset of host genes enriched in the HDAC biological pathway. These circRNAs and parental mRNAs held in common a small collection of miRNA response elements (MREs), some of which were present in HIV-1 mRNAs. The function of the MRE-containing target mRNA enriched the RNA polymerase II GO pathway. To visualize the interplay between individual circRNA-miRNA-target mRNA, important for HIV-1 and potentially other diseases, an Interactive Circos tool was developed to efficiently parse the intricately competing endogenous network of circRNA-miRNA-mRNA interactions originating from seven circRNA singled out in viremic versus non-viremic patients. The combined downregulation of the identified circRNAs warrants investigation as a novel antiviral targeting strategy.
自 1981 年艾滋病毒 1 型/艾滋病（HIV-1/AIDS）疫情爆发以来，已有 7500 万人感染该病毒，该疾病仍然是全球范围内的公共卫生危机。环状 RNA（circRNA）是通过反式剪接从切除的外显子和内含子衍生而来的，反式剪接是一种选择性剪接形式。非常规的、无帽的和非多聚 A 的转录物与转录组学研究的相关性仍有待常规研究。有待填补的知识空白是宿主编码的 circRNA 与慢性进展患者中病毒复制之间的界面，以及在接受抗病毒药物治疗时的界面。我们实施了一个生物信息学管道，并重新利用了以前在 HIV-1 阳性患者的血液中存档的 RNA 序列读数，这些患者的转录组在病毒血症和抗逆转录病毒治疗（ART）抑制病毒血症期间进行了比较。计算机分析确定了在接受 ART 后变得无法检测到的病毒血症患者的 circRNA。这些 circRNA 源自一组富含组蛋白去乙酰化酶（HDAC）生物学途径的宿主基因。这些 circRNA 和其亲本 mRNA 共有一小部分 miRNA 反应元件（MREs），其中一些存在于 HIV-1 mRNA 中。含有 MRE 的靶 mRNA 的功能丰富了 RNA 聚合酶 II GO 途径。为了可视化单个 circRNA-miRNA-靶 mRNA 之间的相互作用，这对于 HIV-1 以及可能其他疾病非常重要，开发了一个交互式 Circos 工具，用于有效地解析源自 7 个在病毒血症与非病毒血症患者中鉴定出的 circRNA 的 circRNA-miRNA-mRNA 相互作用的复杂竞争内源性网络。鉴定出的 circRNA 的综合下调值得作为一种新的抗病毒靶向策略进行研究。
