Activation of the virus-induced IKK/NF-κB signalling axis is critical for the replication of human cytomegalovirus in quiescent cells

Patrizia Caposio, Anna Luganini, Gabriele Hahn, Santo Landolfo, Giorgio Gribaudo

Research output: Contribution to journalArticle

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Abstract

Activation of the IKK/NF-κB signalling pathway is a hallmark of human cytomegalovirus (HCMV) infection. However, its role in regulating major immediate-early promoter (MIEP)-dependent transcription and HCMV replication remains controversial. This study uses a combination of genetic approaches to investigate the effects of cell culture conditions on the importance of virus-induced NF-κB activation during the infection of endothelial cells or fibroblasts. Adenoviral-mediated expression of a dominant-negative mutant of IKK2 kinase (dnIKK2) in human umbilical vein endothelial cells resulted in a strong reduction of IκBα degradation and NF-κB activation following infection with an HCMV clinical isolate. Viral replication was impaired in dnIKK2-expressing cells that were growth-arrested before infection, but not in replicating cells. The inhibitory effect of dnIKK2 was independent from the virus strain and the cell type used, because replication of the laboratory AD169 strain was impaired as well in dnIKK2-expressing quiescent fibroblasts. Moreover, progressive disruption of NF-κB response elements within the MIEP in recombinant HCMV viruses derived from the clinical isolate prevented their replication in quiescent cells but not in actively growing cells. These results demonstrate an essential role of virus-induced IKK/NF-κB activity to trigger both viral IE gene expression and productive replication in quiescent cells.

Original languageEnglish (US)
Pages (from-to)2040-2054
Number of pages15
JournalCellular Microbiology
Volume9
Issue number8
DOIs
StatePublished - Aug 2007
Externally publishedYes

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Virus Activation
Cytomegalovirus
Viruses
Chemical activation
Endothelial cells
Fibroblasts
Response Elements
Transcription
Infection
Cell culture
Gene expression
Phosphotransferases
Viral Genes
Human Umbilical Vein Endothelial Cells
Cytomegalovirus Infections
Degradation
Endothelial Cells
Cell Culture Techniques
Gene Expression
Growth

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Microbiology

Cite this

Activation of the virus-induced IKK/NF-κB signalling axis is critical for the replication of human cytomegalovirus in quiescent cells. / Caposio, Patrizia; Luganini, Anna; Hahn, Gabriele; Landolfo, Santo; Gribaudo, Giorgio.

In: Cellular Microbiology, Vol. 9, No. 8, 08.2007, p. 2040-2054.

Research output: Contribution to journalArticle

Caposio, Patrizia ; Luganini, Anna ; Hahn, Gabriele ; Landolfo, Santo ; Gribaudo, Giorgio. / Activation of the virus-induced IKK/NF-κB signalling axis is critical for the replication of human cytomegalovirus in quiescent cells. In: Cellular Microbiology. 2007 ; Vol. 9, No. 8. pp. 2040-2054.
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