Analysis of the interferon regulatory factor (IRF) and NF-kappaB pathways during the replication of Varicella-zoster virus

• Antragstellerin: Dr. Nathalie Desloges
• Fachliche Zuordnung: Virologie
• Förderung: Förderung von 2005 bis 2008
• Projektkennung: Deutsche Forschungsgemeinschaft (DFG) - Projektnummer 13063109

In response to viral infection, host cells elicit a number of responses to activate defense systems, including the expression of type I interferon (IFN-¿¿/¿). The induction of IFN requires postranslational modifications of latent transcription factors including NF-¿B and the interferon regulatory factor (IRF) 3 (IRF-3). Two I¿B kinase (IKK)-related kinases, IKK¿¿and TBK1, have been identified as virus-induced IRF-3 activators. Moreover, these kinases may modulate aspects of NF-¿B activation. The connection between the IRF-3 and the NF-¿B pathways led us to design a project the activation of these two pathways will be studied in the context of cells infected with Varicella-zoster virus (VZV), a member of the alphaherpesvirus subfamily. We will also investigate whether VZV has developed strategies to block the activation of IRF-3 to counteract the antiviral effect of IFN. IRF-1, IRF-2, and IRF- 7, which are transcription factors of the same family than IRF-3 will be analysed to determine whether these factors are implicated in the induction of IFN later on. Another cell response to virus infection is the induction of apoptosis. NF-¿B seems to be involved in the mechanism that antagonizes the apoptotic response. Its role and the possibility of being modulated by viral factors will be investigated in VZV-infected cells.

• DFG-Verfahren: Sachbeihilfen