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Neutrality of the Canonical NF- B-Dependent Pathway for Human and Murine Cytomegalovirus Transcription and Replication In Vitro

Benedict, C. A., Angulo, A., Patterson, G., Ha, S., Huang, H., Messerle, M., Ware, C. F. and Ghazal, P. 2004. Neutrality of the Canonical NF- B-Dependent Pathway for Human and Murine Cytomegalovirus Transcription and Replication In Vitro. Journal of Virology 78 (2) , pp. 741-750. 10.1128/JVI.78.2.741-750.2004

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Abstract

Cytomegalovirus (CMV) is known to rapidly induce activation of nuclear factor κB (NF-κB) after infection of fibroblast and macrophage cells. NF-κB response elements are present in the enhancer region of the CMV major immediate-early promoter (MIEP), and activity of the MIEP is strongly upregulated by NF-κB in transient-transfection assays. Here we investigate whether the NF-κB-dependent pathway is required for initiating or potentiating human and murine CMV replication in vitro. We show that expression of a dominant negative mutant of the inhibitor of NF-κB-alpha (IκBαM) does not alter the replication kinetics of human or mouse CMV in cultured cells. In addition, mouse embryo fibroblasts genetically deficient for p65/RelA actually showed elevated levels of MCMV replication. Mutation of all NF-κB response elements within the enhancer of the MIEP in a recombinant mouse CMV containing the human MIEP (hMCMV-ES), which we have previously shown to replicate in murine fibroblasts with kinetics equivalent to that of wild-type mouse CMV, did not negatively affect replication in fibroblasts. Taken together, these data show that, for CMV replication in cultured fibroblasts activation of the canonical NF-κB pathway and binding of NF-κB to the MIEP are dispensable, and in the case of p65 may even interfere, thus uncovering a previously unrecognized level of complexity in the host regulatory network governing MIE gene expression in the context of a viral infection.

Item Type: Article
Date Type: Publication
Schools: Medicine
Publisher: American Society for Microbiology
ISSN: 0022-538X
Last Modified: 27 Jul 2018 14:30
URI: http://orca.cf.ac.uk/id/eprint/113496

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