INDUCTION OF INTERFERON-ALPHA GENES EXPRESSION

Type I interferons (IFNA and IFNB) belong to the group of inflammatory cytokines that are expressed in eukaryotic cells as an early response to viral infection. While the IFN B is encoded by a single gene, IFNA are represented by a large family of structurally related genes that are expressed preferentially in cells of lymphoid lineage. The IFNA genes show differential expression as well as cell type specificity which reflects the transcriptional inducibility of the respective promoter regions. Expression of IFNA genes in infected cells is transient, independent of cellular protein synthesis and is inhibited in the presence of tyrosine kinase and protein kinase C inhibitors. The virus response element (VRE) present in the promoter region of these genes functions as a virus-specific enhancer and confers expression in infected cells. Lack of expression of individual murine IFNA genes cen be related both to the presence of the silencing region(s) outside of the VRE as well as to mutations within the VRE. Two overlapping regulatory domains, AF-1 and interferon regulatory factors (IRF-1) play a critical role in the transcriptional activation of the IFNA promoter region by viral infection.