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

<b>Background</b>: 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...

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Main Authors: Yanglan Wang, Mengying Liu, Xing Guo, Bohan Zhang, Hanping Li, Yongjian Liu, Jingwan Han, Lei Jia, Lin Li
Format: Article
Language:English
Published: MDPI AG 2022-12-01
Series:Viruses
Subjects:
Online Access:https://www.mdpi.com/1999-4915/15/1/60
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author Yanglan Wang
Mengying Liu
Xing Guo
Bohan Zhang
Hanping Li
Yongjian Liu
Jingwan Han
Lei Jia
Lin Li
author_facet Yanglan Wang
Mengying Liu
Xing Guo
Bohan Zhang
Hanping Li
Yongjian Liu
Jingwan Han
Lei Jia
Lin Li
author_sort Yanglan Wang
collection DOAJ
description <b>Background</b>: 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. <b>Methods</b>: 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. <b>Results</b>: 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 <i>AIM2</i>, <i>IFIT1</i>, <i>IFIT2</i>, <i>IFIT3</i>, <i>STAT1</i>, and <i>IRF</i> were activated via the JAK–STAT pathway in response to interferon stimulation. Thus, <i>STAT1</i>, <i>STAT2</i>, and <i>IRF1</i> appear to play core roles in regulatory networks and are closely associated with ERVs. <b>Conclusions</b>: The RNA expression of ISGs and ERV elements is correlated, indicating that ERV elements are closely linked to host innate immune responses.
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spelling doaj.art-7ad72ade1f184630aaaf77756b981b072023-12-01T01:07:35ZengMDPI AGViruses1999-49152022-12-011516010.3390/v15010060Endogenous Retrovirus Elements Are Co-Expressed with IFN Stimulation Genes in the JAK–STAT PathwayYanglan Wang0Mengying Liu1Xing Guo2Bohan Zhang3Hanping Li4Yongjian Liu5Jingwan Han6Lei Jia7Lin Li8College of Life Science and Technology, Beijing University of Chemical Technology, Beijing 100029, ChinaCollege of Life Science and Technology, Beijing University of Chemical Technology, Beijing 100029, ChinaDepartment of Virology, Beijing Institute of Microbiology and Epidemiology, Beijing 100071, ChinaDepartment of Virology, Beijing Institute of Microbiology and Epidemiology, Beijing 100071, ChinaDepartment of Virology, Beijing Institute of Microbiology and Epidemiology, Beijing 100071, ChinaDepartment of Virology, Beijing Institute of Microbiology and Epidemiology, Beijing 100071, ChinaDepartment of Virology, Beijing Institute of Microbiology and Epidemiology, Beijing 100071, ChinaDepartment of Virology, Beijing Institute of Microbiology and Epidemiology, Beijing 100071, ChinaDepartment of Virology, Beijing Institute of Microbiology and Epidemiology, Beijing 100071, China<b>Background</b>: 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. <b>Methods</b>: 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. <b>Results</b>: 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 <i>AIM2</i>, <i>IFIT1</i>, <i>IFIT2</i>, <i>IFIT3</i>, <i>STAT1</i>, and <i>IRF</i> were activated via the JAK–STAT pathway in response to interferon stimulation. Thus, <i>STAT1</i>, <i>STAT2</i>, and <i>IRF1</i> appear to play core roles in regulatory networks and are closely associated with ERVs. <b>Conclusions</b>: The RNA expression of ISGs and ERV elements is correlated, indicating that ERV elements are closely linked to host innate immune responses.https://www.mdpi.com/1999-4915/15/1/60IFN-βERVLTRDEHERV-G pairsISGs
spellingShingle Yanglan Wang
Mengying Liu
Xing Guo
Bohan Zhang
Hanping Li
Yongjian Liu
Jingwan Han
Lei Jia
Lin Li
Endogenous Retrovirus Elements Are Co-Expressed with IFN Stimulation Genes in the JAK–STAT Pathway
Viruses
IFN-β
ERV
LTR
DEHERV-G pairs
ISGs
title Endogenous Retrovirus Elements Are Co-Expressed with IFN Stimulation Genes in the JAK–STAT Pathway
title_full Endogenous Retrovirus Elements Are Co-Expressed with IFN Stimulation Genes in the JAK–STAT Pathway
title_fullStr Endogenous Retrovirus Elements Are Co-Expressed with IFN Stimulation Genes in the JAK–STAT Pathway
title_full_unstemmed Endogenous Retrovirus Elements Are Co-Expressed with IFN Stimulation Genes in the JAK–STAT Pathway
title_short Endogenous Retrovirus Elements Are Co-Expressed with IFN Stimulation Genes in the JAK–STAT Pathway
title_sort endogenous retrovirus elements are co expressed with ifn stimulation genes in the jak stat pathway
topic IFN-β
ERV
LTR
DEHERV-G pairs
ISGs
url https://www.mdpi.com/1999-4915/15/1/60
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