The ORF1ab of Feline Coronavirus Plays a Critical Role in Regulating the Innate Immune Response

Feline coronaviruses (FCoVs) are divided into two groups: feline infectious peritonitis virus (FIPV) and feline enteric coronavirus (FECV). FIPV is responsible for the severe disease known as feline infectious peritonitis, while FECV typically causes mild symptoms, such as diarrhea, and often does not lead to any disease at all. Currently, it is not possible to distinguish between FIPV and FECV at the molecular level. Therefore, there is an urgent need to understand the molecular features of FIPV. Here, we generated a recombinant virus by replacing the ORF1ab region and the coding sequence for the spike (S) protein of an FECV with the corresponding sequences from FIPVs. The recombinant virus (recFECV-S_DF-2-1ab_FIPV) exhibited similar growth kinetics to its parental strain. Our analysis revealed that the replacement of the ORF1ab in the FECV caused significant alterations in protein expression within the host cells. Furthermore, the presence of the ORF1ab from the FIPV strain resulted in enhanced suppression of the innate immune response compared to the parental strain, as determined through proteomic and transcriptomic studies. Additionally, we demonstrated that the papain-like protease 2 (PL2^pro) of the non-structural protein 3 (NSP3) from both FIPV and FECV functions in immune suppression, and the protease activity is required for this function.