HIV Cure Research Center, Department of Internal Medicine and Pediatrics, Ghent University and Ghent University Hospital, 9000 Ghent, Belgium.
Division of Microbiology and Immunology, Department of Pathology, University of Utah School of Medicine, Salt Lake City, UT 84132, USA.
Int J Mol Sci. 2020 Oct 19;21(20):7741. doi: 10.3390/ijms21207741.
Interferons play a critical role in the innate immune response against a variety of pathogens, such as HIV-1. Recent studies have shown that long non-coding genes are part of a reciprocal feedforward/feedback relationship with interferon expression. They presumably contribute to the cell type specificity of the interferon response, such as the phenotypic and functional transition of macrophages throughout the immune response. However, no comprehensive understanding exists today about the IFN-lncRNA interplay in macrophages, also a sanctuary for latent HIV-1. Therefore, we completed a poly-A+ RNAseq analysis on monocyte-derived macrophages (MDMs) treated with members of all three types of IFNs (IFN-α, IFN-ε, IFN-γ or IFN-λ) and on macrophages infected with HIV-1, revealing an extensive non-coding IFN and/or HIV-1 response. Moreover, co-expression correlation with mRNAs was used to identify important (long) non-coding hub genes within IFN- or HIV-1-associated gene clusters. This study identified and prioritized IFN related hub lncRNAs for further functional validation.
干扰素在针对多种病原体（如 HIV-1）的先天免疫反应中发挥着关键作用。最近的研究表明，长非编码基因是干扰素表达的一种相互正反馈/负反馈关系的一部分。它们可能有助于干扰素反应的细胞类型特异性，例如巨噬细胞在整个免疫反应中的表型和功能转变。然而，目前对于巨噬细胞中的 IFN-lncRNA 相互作用还没有全面的了解，巨噬细胞也是潜伏 HIV-1 的避难所。因此，我们对用所有三种类型的干扰素（IFN-α、IFN-ε、IFN-γ 或 IFN-λ）处理的单核细胞衍生的巨噬细胞（MDM）以及感染 HIV-1 的巨噬细胞进行了 poly-A+RNAseq 分析，揭示了广泛的非编码 IFN 和/或 HIV-1 反应。此外，与 mRNAs 的共表达相关性用于识别 IFN 或 HIV-1 相关基因簇内的重要（长）非编码枢纽基因。这项研究确定并优先考虑了与 IFN 相关的 hub lncRNAs，以进行进一步的功能验证。
