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

• Published in: The Journal of biological chemistry 2006, Vol.281 (11), p.7110-7117
• Main Authors: Amici, Carla, Rossi, Antonio, Costanzo, Antonio, Ciafrè, Stefania, Marinari, Barbara, Balsamo, Mirna, Levrero, Massimo, Santoro, M. Gabriella
• Format: Article
• Language: English
• ISSN: 0021-9258; 1083-351X

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.