Mutation in Spike Protein Cleavage Site and Pathogenesis of Feline Coronavirus
subject: macrophage, pathology, protease, Protein Processing, Feline coronavirus, Viruses, conserved furin cleavage motif
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.
creator: Beth N. Licitra, Jean K. Millet, Andrew D. Regan, Brian S. Hamilton, Vera D. Rinaldi, Gerald E. Duhamel, Gary R. Whittaker
source: Emerging Infectious Diseases
publisher: Centers for Disease Control and Prevention
date: 2013
language: EN
identifier: DOI: 10.3201/eid1907.121094
coverage: Infectious and parasitic diseases, Medicine