ID: 29: Functional characterization of the human IFNL4 promoter: Roles for Sp1, NF-kB and IRF3/7

Abstract

Interferon Lambda 4 (IFN λ 4) is a recently discovered Type III interferon that has evolved as a pseudogene in the human population. The full-length expression of IFN λ 4 depends on the presence of a frame shift deletion polymorphism, in the first exon of IFNL4, which completes the open reading frame. IFN λ 4 can raise an antiviral state within cells inhibiting the replication of several viruses. The expression of IFN λ 4 could be associated with the pathogenesis mechanisms of several viruses, but how the IFNL4 gene is transcriptionally regulated is not yet studied. In this report we use the lung carcinoma derived cell line A549 that is genetically viable to express a functional IFN λ 4, to address the transcriptional requirements of the IFNL4 promoter. We show that the GC-rich DNA binding transcription factor Sp1 is recruited to the IFNL4 promoter and has a role in induction of gene expression upon stimulation with the viral RNA mimic poly(I:C). By using siRNA mediated knockdown and overexpression strategies we show roles for the virus-associated transcription factors NF- κ B, IRF3 and IRF7, in driving gene expression. These results show that similar to the other Type III interferon genes IFNL4 could be induced by virus -associated transcription factors.