ETV7 acts as a negative regulator of the type I interferon response by preferentially targeting antiviral interferon-stimulated genes, limiting the control of influenza viruses.
ETV7 acts as a negative regulator of the type I interferon response, suggesting it could be a therapeutic target to enhance innate antiviral responses against influenza.
The type I interferon (IFN) response is an important component of the innate immune response to viral infection. Precise control of IFN responses is critical because insufficient expression of IFN-stimulated genes (ISGs) can lead to a failure to restrict viral spread, whereas excessive ISG activation can result in IFN-related pathologies. Although both positive and negative regulatory factors control the magnitude and duration of IFN signaling, it is also appreciated that several ISGs regulate aspects of the IFN response themselves. In this study, we performed a CRISPR activation screen to identify previously unknown regulators of the type I IFN response. We identified the strongly induced ISG encoding ETS variant transcription factor 7 (ETV7) as a negative regulator of the type I IFN response. However, ETV7 did not uniformly suppress ISG transcription. Instead, ETV7 preferentially targeted a subset of antiviral ISGs that were particularly important for IFN-mediated control of influenza viruses. Together, our data assign a function for ETV7 as an IFN response regulator and also identify ETV7 as a potential therapeutic target to increase innate antiviral responses and enhance IFN-based antiviral therapies.
Froggatt et al. (Tue,) conducted a other in Influenza virus infection. ETV7 was evaluated on Identification of regulators of the type I IFN response. ETV7 acts as a negative regulator of the type I interferon response by preferentially targeting antiviral interferon-stimulated genes, limiting the control of influenza viruses.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: