Herpes simplex viruses (HSVs) are able to hijack the host-cell I kappa B kinase (IKK)/NF-kappa B pathway, which regulates critical cell functions from apoptosis to inflammatory responses; however, the molecular mechanisms involved and the outcome of the signaling dysregulation on the host-virus interaction are mostly unknown. Here we show that in human keratinocytes HSV-1 attains a sophisticated control of the IKK/NF-kappa B pathway, inducing two distinct temporally controlled waves of IKK activity and disrupting the NF-kappa B autoregulatory mechanism. Using chromatin immunoprecipitation we demonstrate that dysregulation of the NF-kappa B-response is mediated by a virus-induced block of NF-kappa B recruitment to the promoter of the I kappa B alpha gene, encoding the main NF-kappa B-inhibitor. We also show that HSV-1 redirects NF-kappa B recruitment to the promoter of ICP0, an immediate-early viral gene with a key role in promoting virus replication. The results reveal a new level of control of cellular functions by invading viruses and suggest that persistent NF-kappa B activation in HSV-1-infected cells, rather than being a host response to the virus, may play a positive role in promoting efficient viral replication.

Amici, C., Rossi, A., Costanzo, A., Ciafre, S., Marinari, B., Balsamo, M., et al. (2006). Herpes simplex virus disrupts NF-kappa B regulation by blocking its recruitment on the I kappa B alpha promoter and directing the factor on viral genes. THE JOURNAL OF BIOLOGICAL CHEMISTRY, 281(11), 7110-7117 [10.1074/jbc.M512366200].

Herpes simplex virus disrupts NF-kappa B regulation by blocking its recruitment on the I kappa B alpha promoter and directing the factor on viral genes.

AMICI, CARLA;COSTANZO, ANTONIO;SANTORO, MARIA GABRIELLA
2006-01-01

Abstract

Herpes simplex viruses (HSVs) are able to hijack the host-cell I kappa B kinase (IKK)/NF-kappa B pathway, which regulates critical cell functions from apoptosis to inflammatory responses; however, the molecular mechanisms involved and the outcome of the signaling dysregulation on the host-virus interaction are mostly unknown. Here we show that in human keratinocytes HSV-1 attains a sophisticated control of the IKK/NF-kappa B pathway, inducing two distinct temporally controlled waves of IKK activity and disrupting the NF-kappa B autoregulatory mechanism. Using chromatin immunoprecipitation we demonstrate that dysregulation of the NF-kappa B-response is mediated by a virus-induced block of NF-kappa B recruitment to the promoter of the I kappa B alpha gene, encoding the main NF-kappa B-inhibitor. We also show that HSV-1 redirects NF-kappa B recruitment to the promoter of ICP0, an immediate-early viral gene with a key role in promoting virus replication. The results reveal a new level of control of cellular functions by invading viruses and suggest that persistent NF-kappa B activation in HSV-1-infected cells, rather than being a host response to the virus, may play a positive role in promoting efficient viral replication.
2006
Pubblicato
Rilevanza internazionale
Articolo
Sì, ma tipo non specificato
Settore MED/07 - MICROBIOLOGIA E MICROBIOLOGIA CLINICA
English
Con Impact Factor ISI
Cells; Cytology; Enzyme kinetics; Enzymes; Genes; Genetic engineering; Viruses; Autoregulatory mechanism; Cellular functions; Herpes simplex viruses (HSV); Viral gene; Microbiology; dimer; I kappa B; immunoglobulin enhancer binding protein; immediate early protein; messenger RNA; NF kappaB inhibitor alpha; NF-kappaB inhibitor alpha; primer DNA; prostaglandin A; prostaglandin A1; ubiquitin protein ligase; Vmw110 protein, Human herpesvirus 1; article; autoregulation; chromatin immunoprecipitation; controlled study; herpes simplex; Herpes simplex virus 1; human; human cell; keratinocyte; priority journal; promoter region; virus gene; virus replication; biological model; cell line; chemistry; gene expression regulation; genetic transcription; genetic transfection; genetics; Herpes simplex virus; inflammation; metabolism; plasmid; signal transduction; time; ultraviolet radiation; Western blotting; Human herpesvirus 1; Simplexvirus; Blotting, Western; Cell Line; Chromatin Immunoprecipitation; DNA Primers; Gene Expression Regulation; Genes, Viral; Herpesvirus 1, Human; Humans; I-kappa B Proteins; Immediate-Early Proteins; Inflammation; Keratinocytes; Models, Genetic; NF-kappa B; Plasmids; Promoter Regions (Genetics); Prostaglandins A; RNA, Messenger; Signal Transduction; Simplexvirus; Time Factors; Transcription, Genetic; Transfection; Ubiquitin-Protein Ligases; Ultraviolet Rays
Amici, C., Rossi, A., Costanzo, A., Ciafre, S., Marinari, B., Balsamo, M., et al. (2006). Herpes simplex virus disrupts NF-kappa B regulation by blocking its recruitment on the I kappa B alpha promoter and directing the factor on viral genes. THE JOURNAL OF BIOLOGICAL CHEMISTRY, 281(11), 7110-7117 [10.1074/jbc.M512366200].
Amici, C; Rossi, A; Costanzo, A; Ciafre, S; Marinari, B; Balsamo, M; Levrero, M; Santoro, Mg
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/39057
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