title: Feline coronavirus replication is affected by both cyclophilin A and cyclophilin B.
abstract: Feline coronavirus (FCoV) causes the fatal disease feline infectious peritonitis, which is currently incurable by drug treatment, and no effective vaccines are available. Cyclosporin A (CsA), a cyclophilin (Cyp) inhibitor, inhibits the replication of FCoV in vitro and in vivo as well as the replication of human and animal coronaviruses. However, the mechanism underlying the regulation of coronavirus replication by CsA is unknown. In this study, we analysed the role of Cyps in FCoV replication using knockdown and knockout cells specific to Cyps. Inhibition of CypA and CypB reduced FCoV replication, with replication in knockout cells being much less than that in knockdown cells. Furthermore, the proteins expressed by CypA and CypB harbouring mutations in their respective predicted peptidyl-prolyl cis-transisomerase active sites, which also alter the affinities between Cyps and CsA, inhibited FCoV replication. These findings indicate that the peptidyl-prolyl cis-transisomerase active sites of Cyps might be required for FCoV replication.
authors.affiliation: Department of Veterinary Hygiene, Veterinary School, Nippon Veterinary and Life Science University, 1-7-1 Kyounan, Musashino, Tokyo 180-8602, Japan.
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Tanaka
authors.affiliation: Division of Molecular Virology, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, 4-6-1, Shirokanedai, Minato-ku, Tokyo 108-8639, Japan.
authors.forename: Yuka
authors.initials: Y
authors.lastname: Sato
authors.affiliation: Department of Microbiology, Faculty of Medicine, Juntendo University, Tokyo 113-8421, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Sasaki
mesh_terms: D000818:Animals; D020134:Catalytic Domain; D002415:Cats; D002460:Cell Line; D016765:Coronavirus, Feline / Q000187:drug effects / Q000502:physiology*; D021984:Cyclophilin A / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D021983:Cyclophilins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D016572:Cyclosporine / Q000494:pharmacology; D016766:Feline Infectious Peritonitis / Q000201:enzymology* / Q000821:virology*; D055785:Gene Knockdown Techniques; D014779:Virus Replication / Q000187:drug effects / Q000235:genetics / Q000502:physiology*
chemical_list: C081786:cyclophilin B; D016572:Cyclosporine; D021984:Cyclophilin A; D021983:Cyclophilins