Transplant-induced reactivation of murine cytomegalovirus immediate early gene expression is associated with recruitment of NF-κB and AP-1 to the major immediate early promoter

The Journal of General Virology
Xue-Feng LiuMary Hummel

Abstract

Reactivation of latent human cytomegalovirus is a significant infectious complication of organ transplantation and current therapies target viral replication once reactivation of latent virus has already occurred. The specific molecular pathways that activate viral gene expression in response to transplantation are not well understood. Our studies aim to identify these factors, with the goal of developing novel therapies that prevent transcriptional reactivation in transplant recipients. Murine cytomegalovirus (MCMV) is a valuable model for studying latency and reactivation of CMV in vivo. We previously demonstrated that transplantation of MCMV-latently infected kidneys into allogeneic recipients induces reactivation of immediate early (IE) gene expression and epigenetic reprogramming of the major immediate early promoter (MIEP) within 48 h. We hypothesize that these events are mediated by activation of signalling pathways that lead to binding of transcription factors to the MIEP, including AP-1 and NF-κB. Here we show that transplantation induces rapid activation of several members of the AP-1 and NF-κB transcription factor family and we demonstrate that canonical NF-κB (p65/p50), the junD component of AP-1, and nucleosome rem...Continue Reading

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Citations

Dec 15, 2016·Scientific Reports·Elina VäisänenMaria Söderlund-Venermo
Jul 20, 2018·Current Opinion in Organ Transplantation·Anil DangiXunrong Luo
Sep 12, 2018·Transplant Infectious Disease : an Official Journal of the Transplantation Society·Susanna K TanJane C Tan
Apr 5, 2019·American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons·Zheng ZhangMichael M Abecassis
Jan 31, 2020·Transplantation·Taylor A Heald-SargentMary A Hummel
Aug 14, 2020·Proceedings of the National Academy of Sciences of the United States of America·Benjamin A KrishnaChristine M O'Connor
Apr 17, 2020·Frontiers in Cellular and Infection Microbiology·Eleonora ForteMary Hummel
May 28, 2021·Frontiers in Cellular and Infection Microbiology·Qingluan YangWenhong Zhang

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