Diversity of nsp15-mediated regulation of coronavirus propagation and virulence. There are two patterns that affect the coronavirus virulence, one including TGEV, and the other including FIPV, MERS-CoV, PEDV, HCoV-229E, MHV, and IBV. Previous studies indicated that loss of EndoU activity in MERS-CoV [combined mutation of EndoU and the accessory protein 4a (NS4a) or 4b (NS4b)], PEDV, HCoV-229E, MHV, and IBV, IFN-β expression levels were significantly activated, thereby, reducing their propagation and virulence. However, we found that EnUmt-TGEV- and EnUmt-FIPV-regulated IFN production and propagation were basically consistent with those regulated by the WT strain. Moreover, the propagation ability and virulence of the EnUmt-TGEV and EnUmt-FIPV were not attenuated in piglets and cats.