Mutation in Spike Protein Cleavage Site and Pathogenesis of Feline Coronavirus
Published Date:Jul 2013
Source:Emerg Infect Dis. 19(7):1066-1073.
Keywords:Amino Acid Motifs
Conserved Furin Cleavage Motif
Feline Enteric Coronavirus
Feline Infectious Peritonitis
Feline Infectious Peritonitis Virus
Sequence Analysis, DNA
Spike Glycoprotein, Coronavirus
Description: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.
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