functional genomics and screening
Recorded terms: gene knockout mice; knockout mouse infection
An attenuated influenza A virus engineered to deliver individual artificial small interfering RNAs enables a fitness-based loss-of-function screen inside an infected mouse, and that screen identifies MDA5 as a contributor to the antiviral response to influenza A virus despite the established role of RIG-I as the sensor that induces interferon beta.
IRF7 and ISGF3 engage overlapping interferon-stimulated response elements and drive largely overlapping antiviral transcriptomes, so that a substantial interferon-like gene program is still induced when type I and type III interferon signaling are both absent.
Mice lacking IKKε produce normal interferon-β but fail to induce roughly a third of interferon-stimulated genes, because interferon activates IKKε, which phosphorylates STAT1 at Ser708 and thereby determines whether ISGF3 occupies a subset of response elements.