title: Differential role for low pH and cathepsin-mediated cleavage of the viral spike protein during entry of serotype II feline coronaviruses.
abstract: Feline infectious peritonitis (FIP) is a terminal disease of cats caused by systemic infection with a feline coronavirus (FCoV). FCoV biotypes that cause FIP are designated feline infectious peritonitis virus (FIPV), and are distinguished by their ability to infect macrophages and monocytes. Antigenically similar to their virulent counterparts are FCoV biotypes designated feline enteric coronavirus (FECV), which usually cause only mild enteritis and are unable to efficiently infect macrophages and monocytes. The FCoV spike protein mediates viral entry into the host cell and has previously been shown to determine the distinct tropism exhibited by certain isolates of FIPV and FECV, however, the molecular mechanism underlying viral pathogenesis has yet to be determined. Here we show that the FECV strain WSU 79-1683 (FECV-1683) is highly dependent on host cell cathepsin B and cathepsin L activity for entry into the host cell, as well as on the low pH of endocytic compartments. In addition, both cathepsin B and cathepsin L are able to induce a specific cleavage event in the FECV-1683 spike protein. In contrast, host cell entry by the FIPV strains WSU 79-1146 (FIPV-1146) and FIPV-DF2 proceeds independently of cathepsin L activity and low pH, but is still highly dependent on cathepsin B activity. In the case of FIPV-1146 and FIPV-DF2, infection of primary feline monocytes was also dependent on host cell cathepsin B activity, indicating that host cell cathepsins may play a role in the distinct tropisms displayed by different feline coronavirus biotypes.
authors.affiliation: Department of Microbiology & Immunology, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853, USA.
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Regan
authors.forename: Renata
authors.initials: R
authors.lastname: Shraybman
authors.forename: Rebecca D
authors.initials: RD
authors.lastname: Cohen
authors.forename: Gary R
authors.initials: GR
authors.lastname: Whittaker
mesh_terms: D000643:Ammonium Chloride; D000818:Animals; D002401:Cathepsin B / Q000378:metabolism*; D056668:Cathepsin L; D002403:Cathepsins / Q000378:metabolism*; D002415:Cats; D002460:Cell Line; D016765:Coronavirus, Feline / Q000145:classification* / Q000502:physiology*; D003546:Cysteine Endopeptidases / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D018942:Macrolides; D008562:Membrane Glycoproteins / Q000378:metabolism*; D009000:Monocytes / Q000821:virology; D064370:Spike Glycoprotein, Coronavirus; D014759:Viral Envelope Proteins / Q000378:metabolism*
chemical_list: D018942:Macrolides; D008562:Membrane Glycoproteins; D064370:Spike Glycoprotein, Coronavirus; D014759:Viral Envelope Proteins; D000643:Ammonium Chloride; C057620:bafilomycin A; D002403:Cathepsins; D003546:Cysteine Endopeptidases; D002401:Cathepsin B; D056668:Cathepsin L