Allogeneic transplantation induces expression of cytomegalovirus immediate-early genes in vivo: A model for reactivation from latency

M. Hummel, Z. Zhang, S. Yan, I. Deplaen, P. Golia, T. Varghese, G. Thomas, M. I. Abecassis*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

99 Scopus citations

Abstract

Reactivation of cytomegalovirus (CMV) from latency is a frequent complication of organ transplantation, and the molecular mechanism by which this occurs is unknown. Previous studies have shown that allogeneic stimulation induces reactivation of human CMV (HCMV) in vitro (64). We find that transplantation of vascularized allogeneic kidneys induces murine CMV (MCMV) and HCMV immediate-early (ie) gene expression. This induction is accompanied by increased expression of transcripts encoding inflammatory cytokines, including tumor necrosis factor (TNF), interleukin-2, and gamma interferon, and by activation of NF-κB. TNF alone can substitute for allogeneic transplantation in inducing HCMV and MCMV ie gene expression in some tissues. Our studies suggest that reactivation is a multistep process which is initiated by factors that induce ie gene expression, including TNF and NF-κB. Allogeneic transplantation combined with immunosuppression may be required to achieve complete reactivation in vivo.

Original languageEnglish (US)
Pages (from-to)4814-4822
Number of pages9
JournalJournal of virology
Volume75
Issue number10
DOIs
StatePublished - 2001

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

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