Renal ischemia/reperfusion injury activates the enhancer domain of the human cytomegalovirus major immediate early promoter

Soo Jung Kim, Thomas K. Varghese, Zheng Zhang, Lee C. Zhao, Gail Thomas, Mary Hummel, Michael Abecassis*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

36 Scopus citations

Abstract

Reactivation of latent human cytomegalovirus is of significant concern in immunocompromised transplant patients and is likely to occur through transcriptional activation of immediate early (ie) gene expression through mechanisms that are not well understood. TNF-mediated activation of NF-κB has been proposed to be one pathway leading to transcriptional activation of CMV ie gene expression. Using transgenic mice carrying a lacZ reporter gene under the control of the HCMV major ie promoter/enhancer (MIEP-lacZ mice) and MIEP-lacZ mice deficient in TNF receptor 1 and TNF receptor 2 (MIEP-lac Z TNFR DKO mice), we demonstrate that renal ischemia/reperfusion (I/R) injury activates the HCMV enhancer independently of TNF. Induction of MIEP-lacZ expression was preceded by TNFR-independent formation of reactive oxygen species (ROS), weak and transient activation of NF-K Band strong and sustained activation of AP-1. Our studies show that, in addition to TNF-mediated signaling, TNF-independent signaling induced by I/R injury can contribute to the activation of the HCMV enhancer. This likely occurs through ROS-mediated activation of AP-1. Targeting MAP kinase signaling pathways as well as NF-κB may be of therapeutic value in patients with CMV infection.

Original languageEnglish (US)
Pages (from-to)1606-1613
Number of pages8
JournalAmerican Journal of Transplantation
Volume5
Issue number7
DOIs
StatePublished - Jul 2005

Keywords

  • AP-1
  • Cytomegalovirus
  • Ischemia/reperfusion injury
  • NF-κB
  • ROS
  • Reactivation
  • Virus latency

ASJC Scopus subject areas

  • Immunology and Allergy
  • Transplantation
  • Pharmacology (medical)

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