College of Life Science and Technology, Beijing University of Chemical Technology, Beijing 100029, China.
Department of Virology, Beijing Institute of Microbiology and Epidemiology, Beijing 100071, China.
Viruses. 2022 Dec 24;15(1):60. doi: 10.3390/v15010060.
: Endogenous retrovirus (ERV) elements can act as proximal regulatory elements in promoting interferon (IFN) responses. Previous relevant studies have mainly focused on IFN-stimulated genes (ISGs). However, the role of ERV elements as cis-regulatory motifs in regulating genes of the JAK-STAT pathway remains poorly understood. In our study, we analyzed the changes in ERV elements and genes under both IFN stimulation and blockade of the signaling pathway. : The effects of interferon on cells under normal conditions and knockout of the receptor were compared based on the THP1_IFNAR1_KO and THP1_IFNAR2_mutant cell lines. The correlation between differentially expressed ERVs (DHERVs) and differentially expressed genes (DEGs) as DEHERV-G pairs was explored with construction of gene regulatory networks related to ERV and induced by proinflammatory cytokines. : A total of 430 DEHERV loci and 190 DEGs were identified in 842 DEHERV-G pairs that are common to the three groups. More than 87% of DEHERV-G pairs demonstrated a consistent expression pattern. ISGs such as , , , , , and were activated via the JAK-STAT pathway in response to interferon stimulation. Thus, , , and appear to play core roles in regulatory networks and are closely associated with ERVs. : The RNA expression of ISGs and ERV elements is correlated, indicating that ERV elements are closely linked to host innate immune responses.
内源性逆转录病毒 (ERV) 元件可以作为促进干扰素 (IFN) 反应的近端调节元件。先前的相关研究主要集中在 IFN 刺激基因 (ISGs) 上。然而，ERV 元件作为调节 JAK-STAT 通路基因的顺式调节基序的作用仍知之甚少。在我们的研究中，我们分析了 IFN 刺激和信号通路阻断下 ERV 元件和基因的变化。
基于 THP1_IFNAR1_KO 和 THP1_IFNAR2_mutant 细胞系，比较了干扰素在正常条件下和受体敲除时对细胞的影响。通过构建与 ERV 相关并受促炎细胞因子诱导的基因调控网络，探讨了差异表达的内源性逆转录病毒 (DHERV) 和差异表达基因 (DEG) 作为 DEHERV-G 对之间的相关性。
在三组共有的 842 个 DEHERV-G 对中，共鉴定出 430 个 DEHERV 基因座和 190 个 DEG。超过 87%的 DEHERV-G 对表现出一致的表达模式。ISGs，如 、 、 、 、 和 ，通过 JAK-STAT 通路被干扰素刺激激活。因此， 、 、 和 似乎在调控网络中发挥核心作用，并与 ERV 密切相关。
ISG 和 ERV 元件的 RNA 表达相关，表明 ERV 元件与宿主固有免疫反应密切相关。
