Laboratory of Human Retrovirology and Immunoinformatics, Applied and Development Research Directorate, Frederick National Laboratory for Cancer Research, Frederick, MD 21702, USA.
Int J Mol Sci. 2021 Jan 28;22(3):1290. doi: 10.3390/ijms22031290.
Interleukin-27 (IL-27) is a pleiotropic cytokine that influences the innate and adaptive immune systems. It inhibits viral infection and regulates the expression of microRNAs (miRNAs). We recently reported that macrophages differentiated from human primary monocytes in the presence of IL-27 and human AB serum resisted human immunodeficiency virus (HIV) infection and showed significant autophagy induction. In the current study, the miRNA profiles in these cells were investigated, especially focusing on the identification of novel miRNAs regulated by IL-27-treatment. The miRNA sequencing analysis detected 38 novel miRNAs. Real-time reverse transcription polymerase chain reaction (RT-PCR) analysis confirmed that IL-27 differentially regulated the expression of 16 of the 38 miRNAs. Overexpression of the synthesized miRNA mimics by transfection revealed that miRAB40 had potent HIV-inhibiting and autophagy-inducing properties. B18R, an interferon (IFN)-neutralization protein, partially suppressed both activities, indicating that the two functions were induced via IFN-dependent and -independent pathways. Although the target mRNA(s) of miRAB40 involving in the induction of both functions was unable to identify in this study, the discovery of miRAB40, a potential HIV-inhibiting and autophagy inducing miRNA, may provide novel insights into the miRNA (small none-coding RNA)-mediated regulation of HIV inhibition and autophagy induction as an innate immune response.
白细胞介素-27（IL-27）是一种多功能细胞因子，影响先天和适应性免疫系统。它抑制病毒感染并调节 microRNAs（miRNAs）的表达。我们最近报道称，在 IL-27 和人 AB 血清存在的情况下，从人原代单核细胞分化而来的巨噬细胞抵抗人类免疫缺陷病毒（HIV）感染，并表现出明显的自噬诱导。在本研究中，研究了这些细胞中的 miRNA 谱，特别是关注鉴定由 IL-27 处理调节的新 miRNA。miRNA 测序分析检测到 38 个新的 miRNA。实时逆转录聚合酶链反应（RT-PCR）分析证实，IL-27 差异调节 38 个 miRNA 中的 16 个的表达。转染合成 miRNA 模拟物的过表达表明 miRAB40 具有强大的 HIV 抑制和自噬诱导特性。干扰素（IFN）中和蛋白 B18R 部分抑制了这两种活性，表明这两种功能是通过 IFN 依赖和非依赖途径诱导的。尽管本研究无法确定涉及两种功能诱导的 miRAB40 的靶 mRNA(s)，但发现 miRAB40 是一种潜在的 HIV 抑制和自噬诱导 miRNA，可能为 miRNA（小非编码 RNA）介导的 HIV 抑制和自噬诱导作为先天免疫反应提供新的见解。
