Open AccessTNF Receptor Independent Activation of the Cytomegalovirus Major Immediate Early Enhancer in Response to Transplantation
Author(s) -
Zheng Zhang,
Soo Jung Kim,
Thomas K. Varghese,
Gail D. Thomas,
Mary Hummel,
Michael Abecassis
Publication year - 2008
Publication title -
transplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.45
H-Index - 204
eISSN - 1534-6080
pISSN - 0041-1337
DOI - 10.1097/tp.0b013e318168449c
Subject(s) - enhancer , tumor necrosis factor alpha , reporter gene , biology , transplantation , receptor , human cytomegalovirus , transcription factor , immunology , microbiology and biotechnology , gene , gene expression , virus , medicine , genetics
Reactivation of latent human cytomegalovirus (HCMV) infection is a significant risk factor for long term allograft dysfunction. The molecular pathways involved in reactivation of latent virus have not been identified. Previous studies suggested that tumor necrosis factor (TNF) -mediated activation of nuclear factor of kappa light polypeptide gene enhancer in B-cells (NF-kappa B) leading to transcriptional reactivation of viral immediate early (ie) gene expression might be important in transplant-associated viral reactivation. CMV IE gene expression is controlled by the major immediate early promoter/enhancer (MIEP). Because HCMV does not infect mice, transgenic mice carrying a beta-galactosidase reporter gene under the control of the HCMV immediate early enhancer (MIEP-lacZ mice) are a valuable model for studying regulation of CMV IE gene expression in vivo. We have used TNF receptor-deficient MIEP-lacZ (MIEP-lacZ TNFR DKO) mice to study the requirement for TNF in transplant-induced activation of the MIEP.