Title

Development of the interferon system in chicken embryo cells: Role of transcription factors IRF-1 and NF-kB, and interferon-inducibility factor

Date of Completion

January 2002

Keywords

Biology, Cell

Degree

Ph.D.

Abstract

Chicken embryo cells (CEC) acquire the enhanced interferon (IFN) inducibility and sensitivity to interferon action with the development of the gestational age (Sekellick et al., 1990). Interferon regulatory factor 1 (IRF-1) and nuclear factor kappa B (NF-kB) are transcription factors which are involved in the transcriptional activation of IFN genes in mammalian cells. ^ The primary goal of this thesis is to examine the role of IRF-1 and NF-kB in the developmentally regulated chicken interferon system, and in turn to understand the role of both transcription factors in the transcriptional regulation of chicken interferon genes and the interferon signaling pathway. Both IRF-1 mRNA and the DNA-binding activity of NF-kB are induced in CEC shortly following UV-irradiated Avian Reovirus (UVARV) infection. The levels of IRF-1 mRNA and the activity of NF-kB reflect the IFN inducing capacity of CEC under different conditions. The interferon-inducing viruses induce the expression of IRF-1 and the NF-kB activity. However, interferon induction-suppressing viruses alone, or in combination with interferon-inducing viruses suppress the expression of both transcription factors. Furthermore, IRF-1 and NF-kB are shown to be involved in the interferon signaling pathway in CEC. Treatment with type I or type II chicken IFNs results in the expression of IRF-1 and NF-kB DNA-binding activity, thereby suggesting the involvement of both IRF-1 and NF-kB in IFN signaling pathway. It is likely that the double-stranded RNA-dependent protein kinase (PKR) mediated NF-kB activation induces the expression of chicken IRF-1 which subsequently activates IFN production in virus-infected CEC. Chicken IRF-1 in turn facilitates the degradation of IkBα and activation of NF-kB in CEC. The newly synthesized chicken IFN may be involved in the autoregulatory mechanisms of IRF-1 and NF-kB by inducing the transcription of the PKR gene. ^ The developmentally regulated chicken IFN system is mediated by the postulated interferon-inducibility factor(s) secreted by CEC during in vitro aging. The biological properties of the interferon-inducibility factor(s) have been characterized in term of its effect on the acquisition of interferon inducibility in developing chicken embryo cells. ^