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TNF receptor independent activation of the cytomegalovirus major immediate early enhancer in response to transplantation.
Transplantation. 2008 Apr 15; 85(7):1039-45.T

Abstract

BACKGROUND

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.

METHODS

Allogenic kidney transplants were performed using MIEP-lacZ TNFR DKO or MIEP-lacZ TNFRwild-type donor mice. beta-Galactosidase activity was used to measure activation of the IE enhancer in donor kidneys at 2 days of posttransplantation and in contralateral controls. Transcription factor activation was assayed with Trans-Am kits.

RESULTS

Allogenic and syngenic transplantation activate the HCMV IE enhancer to the same extent. TNF receptor signaling was not required for activation of the MIEP. TNF receptor signaling was required for activation of NF-kappaB, but not for activation of activating protein 1 family members junD and Fra-1 in day 2 allografts.

CONCLUSIONS

TNF-independent pathways can activate the enhancer in response to allogenic transplantation. This may occur through activation of MIEP-binding transcription factors other than NF-kappa B.

Authors+Show Affiliations

Transplant Division, Department of Surgery, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

18408586

Citation

Zhang, Zheng, et al. "TNF Receptor Independent Activation of the Cytomegalovirus Major Immediate Early Enhancer in Response to Transplantation." Transplantation, vol. 85, no. 7, 2008, pp. 1039-45.
Zhang Z, Kim SJ, Varghese T, et al. TNF receptor independent activation of the cytomegalovirus major immediate early enhancer in response to transplantation. Transplantation. 2008;85(7):1039-45.
Zhang, Z., Kim, S. J., Varghese, T., Thomas, G., Hummel, M., & Abecassis, M. (2008). TNF receptor independent activation of the cytomegalovirus major immediate early enhancer in response to transplantation. Transplantation, 85(7), 1039-45. https://doi.org/10.1097/TP.0b013e318168449c
Zhang Z, et al. TNF Receptor Independent Activation of the Cytomegalovirus Major Immediate Early Enhancer in Response to Transplantation. Transplantation. 2008 Apr 15;85(7):1039-45. PubMed PMID: 18408586.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - TNF receptor independent activation of the cytomegalovirus major immediate early enhancer in response to transplantation. AU - Zhang,Zheng, AU - Kim,Soo Jung, AU - Varghese,Thomas, AU - Thomas,Gail, AU - Hummel,Mary, AU - Abecassis,Michael, PY - 2008/4/15/pubmed PY - 2008/8/12/medline PY - 2008/4/15/entrez SP - 1039 EP - 45 JF - Transplantation JO - Transplantation VL - 85 IS - 7 N2 - BACKGROUND: 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. METHODS: Allogenic kidney transplants were performed using MIEP-lacZ TNFR DKO or MIEP-lacZ TNFRwild-type donor mice. beta-Galactosidase activity was used to measure activation of the IE enhancer in donor kidneys at 2 days of posttransplantation and in contralateral controls. Transcription factor activation was assayed with Trans-Am kits. RESULTS: Allogenic and syngenic transplantation activate the HCMV IE enhancer to the same extent. TNF receptor signaling was not required for activation of the MIEP. TNF receptor signaling was required for activation of NF-kappaB, but not for activation of activating protein 1 family members junD and Fra-1 in day 2 allografts. CONCLUSIONS: TNF-independent pathways can activate the enhancer in response to allogenic transplantation. This may occur through activation of MIEP-binding transcription factors other than NF-kappa B. SN - 0041-1337 UR - https://www.unboundmedicine.com/medline/citation/18408586/TNF_receptor_independent_activation_of_the_cytomegalovirus_major_immediate_early_enhancer_in_response_to_transplantation_ L2 - https://doi.org/10.1097/TP.0b013e318168449c DB - PRIME DP - Unbound Medicine ER -