NF-kappaB activation can mediate inhibition of human cytomegalovirus replication

The activation of NF-kappaB has long been considered a positive factor for human cytomegalovirus (HCMV) replication. The HCMV immediate-early promoter, the initial transcriptional element in the HCMV replication cycle, is activated by the transcription factor NF-kappaB, and several HCMV gene product...

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Bibliographic Details
Published in:Journal of general virology 2005-02, Vol.86 (Pt 2), p.285-295
Main Authors: Eickhoff, Jan Eike, Cotten, Matt
Format: Article
Language:English
Subjects:
Animals
Cells, Cultured
Cytomegalovirus - immunology
Cytomegalovirus - physiology
Fibroblasts
Humans
I-kappa B Kinase
Interferon-beta - metabolism
Mice
NF-kappa B - physiology
Protein-Serine-Threonine Kinases - metabolism
Signal Transduction
Virus Replication
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Summary:The activation of NF-kappaB has long been considered a positive factor for human cytomegalovirus (HCMV) replication. The HCMV immediate-early promoter, the initial transcriptional element in the HCMV replication cycle, is activated by the transcription factor NF-kappaB, and several HCMV gene products have been demonstrated to activate this transcription factor. However, the role of NF-kappaB in the full replication cycle of the virus has not been carefully examined. A series of experiments that demonstrate an important inhibitory role of NF-kappaB for HCMV replication in fibroblasts is presented here. Using both genetic and pharmaceutical methods, it was shown that blocking NF-kappaB activation in cell culture does not inhibit HCMV replication, but rather leads to a modest increase in replication. Two cytokines inhibitory for HCMV, tumour necrosis factor-alpha and interferon-gamma, no longer inhibit HCMV when NF-kappaB activation is blocked. Furthermore, forced expression of the NF-kappaB activating IkappaB kinase beta (IKKbeta), but not a kinase inactive mutant, also inhibits HCMV replication. In addition, it was shown that NF-kappaB signalling is essential for the production of an anti-viral factor in the supernatant of HCMV-infected fibroblasts, and identified interferon-beta as this factor. Thus, the role of NF-kappaB in fibroblasts is to activate a host defence against HCMV.
ISSN:0022-1317
DOI:10.1099/vir.0.80458-0