Spike protein fusion peptide and feline coronavirus virulence.
Coronaviruses are well known for their potential to change their host or tissue tropism, resulting in unpredictable new diseases and changes in pathogenicity; severe acute respiratory syndrome and feline coronaviruses, respectively, are the most recognized examples. Feline coronaviruses occur as 2 pathotypes: nonvirulent feline enteric coronaviruses (FECVs), which replicate in intestinal epithelium cells, and lethal feline infectious peritonitis viruses (FIPVs), which replicate in macrophages. Evidence indicates that FIPV originates from FECV by mutation, but consistent distinguishing differences have not been established. We sequenced the full genome of 11 viruses of each pathotype and then focused on the single most distinctive site by additionally sequencing hundreds of viruses in that region. As a result, we identified 2 alternative amino acid differences in the putative fusion peptide of the spike protein that together distinguish FIPV from FECV in >95% of cases. By these and perhaps other mutations, the virus apparently acquires its macrophage tropism and spreads systemically.
Virology Division, Department of Infectious Diseases and Immunology, Veterinary Faculty, Utrecht University, Utrecht, the Netherlands.
Hui-Wen
HW
Chang
Herman F
HF
Egberink
Rebecca
R
Halpin
David J
DJ
Spiro
Peter J M
PJ
Rottier
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002415:Cats; D018352:Coronavirus Infections / Q000821:virology; D016765:Coronavirus, Feline / Q000235:genetics / Q000378:metabolism / Q000472:pathogenicity*; D016766:Feline Infectious Peritonitis / Q000821:virology; D016679:Genome, Viral; D008562:Membrane Glycoproteins / Q000235:genetics* / Q000378:metabolism; D008969:Molecular Sequence Data; D009154:Mutation; D010455:Peptides / Q000235:genetics*; D011993:Recombinant Fusion Proteins / Q000235:genetics*; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D064370:Spike Glycoprotein, Coronavirus; D014759:Viral Envelope Proteins / Q000235:genetics* / Q000378:metabolism; D014774:Virulence / Q000235:genetics
D008562:Membrane Glycoproteins; D010455:Peptides; D011993:Recombinant Fusion Proteins; D064370:Spike Glycoprotein, Coronavirus; D014759:Viral Envelope Proteins