Feline coronaviruses (FCoV) exist as 2 biotypes: feline enteric coronavirus (FECV) and feline infectious peritonitis virus (FIPV)FECV causes subclinical infections; FIPV causes feline infectious peritonitis (FIP), a systemic and fatal diseaseIt is thought that mutations in FECV enable infection of macrophages, causing FIPHowever, the molecular basis for this biotype switch is unknownWe examined a furin cleavage site in the region between receptor-binding (S1) and fusion (S2) domains of the spike of serotype 1 FCoVFECV sequences were compared with FIPV sequencesAll FECVs had a conserved furin cleavage motifFor FIPV, there was a correlation with the disease and >1 substitution in the S1/S2 motifFluorogenic peptide assays confirmed that the substitutions modulate furin cleavageWe document a functionally relevant S1/S2 mutation that arises when FIP develops in a catThese insights into FIP pathogenesis may be useful in development of diagnostic, prevention, and treatment measures against coronaviruses.
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