Figure 9. Proposed model of the species-specific inhibition of RIG-I by influenza A virus NS1 protein.

The NS1 proteins of avian influenza viruses bind to chicken TRIM25, thereby suppressing IFN induction. The substrate of TRIM25 in avian cells has yet to be determined. The NS1 proteins from human influenza viruses bind to and inhibit both human TRIM25 and human Riplet, thereby suppressing the ubiquitination of the RIG-I CARD and CTD. The NS1 proteins from avian, human and mouse-adapted influenza viruses block Riplet but not TRIM25 for the inhibition of RIG-I signaling in mouse cells.