Key message
Our data highlight hepatocytes, and not immune cells, as main type I interferon producers and sensors, which in the mouse are relevant for the control of CVB3 infection. Similarly, also in vitro CVB3 infection studies with human hepatocytes revealed a more dominant role of the IFN-I than the IFN-III axis for proper ISG induction.
Translational perspective
Our observation, that hepatic IFN-I is critical to control CVB3 infection, motivates to search for defects in the IFN-I induction and IFNAR signaling pathways in fatal cases of neonatal hepatocyte necrosis. Furthermore, our findings can help to better understand the impact of hepatic IFN-β on myocarditis and other CVB3-associated diseases, which has to be further analyzed.