Transcription Factor Redundancy Ensures Induction of the Antiviral State

Transcriptional response to virus infection in mice lacking type I and type III signaling The transcriptional response to virus infection is thought to be predominantly induced by interferon (IFN) signaling. Here we demonstrate that, in the absence of IFN signaling, an IFN-like transcriptome is still maintained. This transcriptional activity is mediated from IFN-stimulated response elements (ISREs) that bind to both the IFN stimulated gene factor 3 (ISGF3) as well as to IFN response factor 7 (IRF7). Through a combination of both in vitro biochemistry and in vivo transcriptional profiling, we have dissected what constitutes IRF-specific, ISGF3-specific, or universal ISREs. Taken together, the data presented here suggests that IRF7 can induce an IFN-like transcriptome in the absence of type-I or -III signaling and therefore provides a level of redundancy to cells to ensure the induction of the antiviral state. Mouse: Infections were performed in triplicate and lungs from each condition were pooled for total RNA isolation. Human: Analysis of IRF7 transcriptome in U3A cell line was performed in duplicates.