TNF-alpha signaling is not required for in vivo transcriptional reactivation of latent murine cytomegalovirus.
BACKGROUND
Reactivation of cytomegalovirus (CMV) is frequently observed in recipients of solid organs and bone marrow transplants and is associated with increased risk of acute and chronic allograft rejection, opportunistic infection, graft failure, and patient mortality. The molecular mechanisms by which reactivation occurs are not well understood. Previous studies have suggested that tumor necrosis factor (TNF)-alpha, which is induced by allogeneic transplantation, may have a role in reactivation of CMV through activation of nuclear factor kappa-light-chain-enhancer of activated B cells and subsequent transcriptional reactivation of immediate early (ie) gene expression.


RESULTS
We have tested the role of TNF-alpha in the reactivation of CMV directly by testing whether TNF-alpha is required to initiate transcription of ie gene expression in a murine model of allogeneic transplantation of kidneys latently infected with mouse CMV.


CONCLUSIONS
Our studies show that although TNF-alpha seems to be sufficient, it is not required for initiating transcription of ie gene expression in this model, suggesting that both TNF-alpha-dependent and -independent pathways play an important role in the reactivation of latent CMV infection.
Zhang
Zheng
Z
Division of Organ Transplantation, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
Li
Zhigao
Z
Yan
Shixian
S
Wang
Xueqiong
X
Abecassis
Michael
M
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology / Q000821:virology*; D003586:Cytomegalovirus Infections / Q000378:metabolism; D005786:Gene Expression Regulation; D006084:Graft Rejection; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D008954:Models, Biological; D018146:Muromegalovirus / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism; D015398:Signal Transduction; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha