In our study, we are the first to generate PARP9 KO mice and PARP9/MAVS DKO mice and demonstrate PARP9 alone, serving as a noncanonical and MAVS-independent RNA sensor, is essential for type I IFN production and plays an important role in antiviral host defense against infection with RNA viruses both in vitro and in vivo. This evidence concerns the gene PARP9 and infection.