Mutation in Spike Protein Cleavage Site and Pathogenesis of Feline Coronavirus
macrophage, pathology, protease, Protein Processing, Feline coronavirus, Viruses, conserved furin cleavage motif
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.
Beth N. Licitra, Jean K. Millet, Andrew D. Regan, Brian S. Hamilton, Vera D. Rinaldi, Gerald E. Duhamel, Gary R. Whittaker
Centers for Disease Control and Prevention
Infectious and parasitic diseases, Medicine