title: Mutation in spike protein cleavage site and pathogenesis of feline coronavirus.
abstract: 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.
authors.affiliation: Cornell University College of Veterinary Medicine,Ithaca, New York 14853, USA.
authors.forename: Beth N
authors.initials: BN
authors.lastname: Licitra
authors.forename: Jean K
authors.initials: JK
authors.lastname: Millet
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Regan
authors.forename: Brian S
authors.initials: BS
authors.lastname: Hamilton
authors.forename: Vera D
authors.initials: VD
authors.lastname: Rinaldi
authors.forename: Gerald E
authors.initials: GE
authors.lastname: Duhamel
authors.forename: Gary R
authors.initials: GR
authors.lastname: Whittaker
mesh_terms: D020816:Amino Acid Motifs; D000818:Animals; D002415:Cats; D017124:Conserved Sequence; D016765:Coronavirus, Feline / Q000235:genetics* / Q000472:pathogenicity; D005243:Feces / Q000821:virology; D016766:Feline Infectious Peritonitis / Q000821:virology*; D009154:Mutation; D059748:Proteolysis; D017422:Sequence Analysis, DNA; D064370:Spike Glycoprotein, Coronavirus / Q000737:chemistry / Q000235:genetics*
chemical_list: D064370:Spike Glycoprotein, Coronavirus
keywords: FECV; FIP; FIPV; Macrophage; conserved furin cleavage motif; feline coronavirus; feline enteric coronavirus; feline infectious peritonitis; feline infectious peritonitis virus; pathology; protease; protein processing; viruses