Endogenous Retrovirus Elements Are Co-Expressed with IFN Stimulation Genes in the JAK–STAT Pathway

Background: 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. Methods: 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. Results: 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 AIM2, IFIT1, IFIT2, IFIT3, STAT1, and IRF were activated via the JAK–STAT pathway in response to interferon stimulation. Thus, STAT1, STAT2, and IRF1 appear to play core roles in regulatory networks and are closely associated with ERVs. Conclusions: The RNA expression of ISGs and ERV elements is correlated, indicating that ERV elements are closely linked to host innate immune responses.