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.
Tipologia: | Articolo su rivista |
Citazione: | 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. |
IF: | Con Impact Factor ISI |
Lingua: | English |
Settore Scientifico Disciplinare: | Settore MED/07 - Microbiologia e Microbiologia Clinica |
Revisione (peer review): | Sì, ma tipo non specificato |
Tipo: | Articolo |
Rilevanza: | Rilevanza internazionale |
Digital Object Identifier (DOI): | 10.1074/jbc.M512366200 |
Stato di pubblicazione: | Pubblicato |
Data di pubblicazione: | 2006 |
Titolo: | 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. |
Autori: | |
Autori: | Amici, C; Rossi, A; Costanzo, A; Ciafre, S; Marinari, B; Balsamo, M; Levrero, M; Santoro, MG |
Appare nelle tipologie: | 01 - Articolo su rivista |