Inherently variable responses to glucocorticoid stress among endogenous retroviruses isolated from 23 mouse strains

Karen Hsu, Young Kwan Lee, Alex Chew, Sophia Chiu, Debora Lim, David G Greenhalgh, Kiho Cho

Research output: Contribution to journalArticle

2 Scopus citations

Abstract

Active participation of endogenous retroviruses (ERVs) in disease processes has been exemplified by the finding that the HERV (human ERV)-W envelope protein is involved in the pathogenesis of multiple sclerosis, an autoimmune disease. We also demonstrated that injury-elicited stressors alter the expression of murine ERVs (MuERVs), both murine leukemia virus-type and mouse mammary tumor virus (MMTV)-type (MMTV-MuERV). In this study, to evaluate MMTV-MuERVs' responses to stress (e.g., injury, infection)-elicited systemic glucocorticoid (GC) levels, we examined the GC-stress response of 64 MMTV-MuERV promoters isolated from the genomes of 23 mouse strains. All 64 promoters responded to treatment with a synthetic GC, dexamethasone (DEX), at a wide range from a 0.6- to 85.7-fold increase in reporter activity compared to no treatment. An analysis of the 10 lowest and 10 highest DEX responders revealed specific promoter elements exclusively present in either the three lowest or the two highest responders. Each promoter had a unique profile of transcription regulatory elements and the glucocorticoid response element (GRE) was identified in all promoters with the number of GREs ranging from 2 to 7. The three lowest DEX responders were the only promoters with two GREs. The findings from this study suggest that certain MMTV-MuERVs are more responsive to stress-elicited systemic GC elevation compared to the others. The mouse strain-specific genomic MMTV-MuERV profiles and individual MMTV-MuERVs' differential responses to GC-stress might explain, at least in part, the variable inflammatory responses to injury and/or infection, often observed among different mouse strains.

Original languageEnglish (US)
JournalBiochimica et Biophysica Acta - Molecular Basis of Disease
DOIs
StateAccepted/In press - Aug 1 2016

Keywords

  • Endogenous retrovirus
  • Glucocorticoid
  • Glucocorticoid response element
  • Inflammation
  • Injury
  • Mouse mammary tumor virus

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology

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