EXPRESS: Identification of within-host deletions in domain 0 of the spike gene of pathogenic feline coronavirus type 2 from the United States.

ObjectivesFeline coronavirus (FCoV) is widely acknowledged to gain pathogenicity within-host to cause the lethal disease feline infectious peritonitis (FIP). Most FIP cases are caused by viruses in genotype 1 (FCoV-1) via an 'internal mutation' in the spike gene. Genotype 2 (FCoV-2) has risen to prominence based on the emergence of FCoV-23, a highly pathogenic novel variant from Cyprus that has a deletion in the N-terminus (domain 0) of spike. In this study, we conducted a retrospective analysis of three cases of FCoV-2 in the U.S.: two (#344 and #346) from 2013 and one (#597) from 2016. Cats #344 and #597 exhibited clinical signs consistent with FCoV infection for at least 2 months. The third cat (#346), the daughter of #344, was euthanized shortly after showing signs.MethodsWe collected a total of 20 tissue, fluid, and fecal samples from the three cats. We characterized the FCoV-2 in these samples using whole-genome sequencing, genetic and phylogenetic analyses, and viral RNA quantification.ResultsWhole-genome sequencing revealed that the two cats exhibiting long-term signs of FIP (#344 and #597) each had a distinct deletion in domain 0 of spike, which was present in all examined tissues. Cat #346, the daughter of #344, which only displayed signs for a short period, had an intact (or long) spike gene. Low RNA titers of the FCoV-2 with the short version were detected in the feces of cats #344 and #597 (2.52 to 5.28 RNA copies/μl).Conclusions and relevanceOur data are consistent with a model whereby FCoV-2 displaying the long version of S is transmitted between cats, while the short version is generated within each cat after a prolonged infection and spreads rapidly throughout the body. We suggest that the high pathogenicity of FCoV-2 is associated with an "internal deletion" in the spike gene.