Human cytomegalovirus attenuates interleukin-1β and tumor necrosis factor alpha proinflammatory signaling by inhibition of NF-κB activation

Michael A. Jarvis, Jamie A. Borton, Amy M. Keech, John Wong, William J. Britt, Bruce E. Magun, Jay Nelson

Research output: Contribution to journalArticle

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Abstract

Viral infection is associated with a vigorous inflammatory response characterized by cellular infiltration and release of the proinflammatory cytokines interleukin-1 (IL-1) and tumor necrosis factor alpha (TNF-α). In the present study, we identified a novel function of human cytomegalovirus (HCMV) that results in inhibition of IL-1 and TNF-α signaling pathways. The effect on these pathways was limited to cells infected with the virus, occurred at late times of infection, and was independent of cell type or virus strain. IL-1 and TNF-α signaling pathways converge at a point upstream of NF-αB activation and involve phosphorylation and degradation of the NF-κB inhibitory molecule IκBα. The HCMV inhibition of IL-1 and TNF-α pathways corresponded to a suppression of NF-κB activation. Analysis of IκBaα phosphorylation and degradation suggested that HCMV induced two independent blocks in NF-κB activation, which occurred upstream from the point of convergence of the IL-1 and TNF-α pathways. We believe that the ability of HCMV to inhibit these two major proinflammatory pathways reveals a critical aspect of HCMV biology, with possible importance for immune evasion, as well as establishment of infection in cell types persistently infected by this virus.

Original languageEnglish (US)
Pages (from-to)5588-5598
Number of pages11
JournalJournal of Virology
Volume80
Issue number11
DOIs
StatePublished - Jun 2006

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Human herpesvirus 5
interleukin-1
Cytomegalovirus
Interleukin-1
tumor necrosis factor-alpha
Tumor Necrosis Factor-alpha
Viruses
viruses
phosphorylation
Phosphorylation
infection
immune evasion
Immune Evasion
degradation
Virus Diseases
cells
Infection
cytokines
inflammation
Cytokines

ASJC Scopus subject areas

  • Immunology

Cite this

Human cytomegalovirus attenuates interleukin-1β and tumor necrosis factor alpha proinflammatory signaling by inhibition of NF-κB activation. / Jarvis, Michael A.; Borton, Jamie A.; Keech, Amy M.; Wong, John; Britt, William J.; Magun, Bruce E.; Nelson, Jay.

In: Journal of Virology, Vol. 80, No. 11, 06.2006, p. 5588-5598.

Research output: Contribution to journalArticle

Jarvis, Michael A. ; Borton, Jamie A. ; Keech, Amy M. ; Wong, John ; Britt, William J. ; Magun, Bruce E. ; Nelson, Jay. / Human cytomegalovirus attenuates interleukin-1β and tumor necrosis factor alpha proinflammatory signaling by inhibition of NF-κB activation. In: Journal of Virology. 2006 ; Vol. 80, No. 11. pp. 5588-5598.
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