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|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 interni:||LEVRERO, Massimo|
|Data di pubblicazione:||2006|
|Rivista:||THE JOURNAL OF BIOLOGICAL CHEMISTRY|
|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.|
|Appare nelle tipologie:||01.a Pubblicazione su Rivista|
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