Feline infectious peritonitis (FIP) is one of the most important infectious 
diseases in cats and is caused by feline coronavirus (FCoV). Tissue 
culture-adapted type I FCoV shows reduced FIP induction in experimental 
infections, which complicates the understanding of FIP pathogenesis caused by 
type I FCoV. We previously found that the type I FCoV strain C3663 efficiently 
induces FIP in specific-pathogen-free cats through the naturally infectious 
route. In this study, we employed a bacterial artificial chromosome-based 
reverse genetics system to gain more insights into FIP caused by the C3633 
strain. We successfully generated recombinant virus (rC3663) from Fcwf-4 cells 
transfected with infectious cDNA that showed growth kinetics similar to those 
shown by the parental virus. Next, we constructed a reporter C3663 virus 
carrying the nanoluciferase (Nluc) gene to measure viral replication with high 
sensitivity. The inhibitory effects of different compounds against rC3663-Nluc 
could be measured within 24 h postinfection. Furthermore, we found that A72 
cells derived from canine fibroblasts permitted FCoV replication without 
apparent cytopathic effects. Thus, our reporter virus is useful for uncovering 
the infectivity of type I FCoV in different cell lines, including canine-derived 
cells. Surprisingly, we uncovered aberrant viral RNA transcription of rC3663 in 
A72 cells. Overall, we succeeded in obtaining infectious cDNA clones derived 
from type I FCoV that retained its virulence. Our recombinant FCoVs are powerful 
tools for increasing our understanding of the viral life cycle and pathogenesis 
of FIP-inducing type I FCoV.IMPORTANCE Feline coronavirus (FCoV) is one of the 
most significant coronaviruses, because this virus induces feline infectious 
peritonitis (FIP), which is a lethal disease in cats. Tissue culture-adapted 
type I FCoV often loses pathogenicity, which complicates research on type I 
FCoV-induced feline infectious peritonitis (FIP). Since we previously found that 
type I FCoV strain C3663 efficiently induces FIP in specific-pathogen-free cats, 
we established a reverse genetics system for the C3663 strain to obtain 
recombinant viruses in the present study. By using a reporter C3663 virus, we 
were able to examine the inhibitory effect of 68 compounds on C3663 replication 
in Fcwf-4 cells and infectivity in a canine-derived cell line. Interestingly, 
one canine cell line, A72, permitted FCoV replication but with low efficiency 
and aberrant viral gene expression.