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 disease. It is thought that mutations in FECV enable infection of macrophages, causing FIP. However, the molecular basis for this biotype switch is unknown. We examined a furin cleavage site in the region between receptor-binding (S1) and fusion (S2) domains of the spike of serotype 1 FCoV. FECV sequences were compared with FIPV sequences. All FECVs had a conserved furin cleavage motif. For FIPV, there was a correlation with the disease and > 1 substitution in the S1/S2 motif. Fluorogenic peptide assays confirmed that the substitutions modulate furin cleavage. We document a functionally relevant S1/S2 mutation that arises when FIP develops in a cat. These insights into FIP pathogenesis may be useful in development of diagnostic, prevention, and treatment measures against coronaviruses.
【저자키워드】 viruses, Macrophage, pathology, protease, Feline infectious peritonitis, Feline coronavirus, Feline infectious peritonitis virus, FIP, FIPV, feline enteric coronavirus, protein processing, FECV, conserved furin cleavage motif, 【초록키워드】 Treatment, Coronaviruses, coronavirus, Mutation, Pathogenesis, macrophages, furin, spike, Infection, diagnostic, peptide, virus, furin cleavage site, cleavage, infectious, assay, correlation, serotype, domain, sequence, S1/S2, measure, Substitution, molecular basis, motif, fatal disease, furin cleavage motif, thought, compared, develop, examined, conserved, the disease, coronavirus, modulate, cause, Site, arise,