title: Requirement for cyclophilin A for the replication of vesicular stomatitis virus New Jersey serotype.
abstract: Several host proteins have been shown to play key roles in the life-cycle of vesicular stomatitis virus (VSV). We have identified an additional host protein, cyclophilin A (CypA), a chaperone protein possessing peptidyl cis-trans prolyl-isomerase activity, as one of the cellular factors required for VSV replication. Inhibition of the enzymatic activity of cellular CypA by cyclosporin A (CsA) or SDZ-211-811 resulted in a drastic inhibition of gene expression by VSV New Jersey (VSV-NJ) serotype, while these drugs had a significantly reduced effect on the genome expression of VSV Indiana (VSV-IND) serotype. Overexpression of a catalytically inactive mutant of CypA resulted in the reduction of VSV-NJ replication, suggesting a requirement for functional CypA for VSV-NJ infection. It was also shown that CypA interacted with the nucleocapsid (N) protein of VSV-NJ and VSV-IND in infected cells and was incorporated into the released virions of both serotypes. VSV-NJ utilized CypA for post-entry intracellular primary transcription, since inhibition of CypA with CsA reduced primary transcription of VSV-NJ by 85-90 %, whereas reduction for VSV-IND was only 10 %. Thus, it seems that cellular CypA binds to the N protein of both serotypes of VSV. However, it performs an obligatory function on the N protein activity of VSV-NJ, while its requirement is significantly less critical for VSV-IND N protein function. The different requirements for CypA by two serologically different viruses belonging to the same family has highlighted the utilization of specific host factors during their evolutionary lineages.
authors.affiliation: Department of Virology, Lerner Research Institute, Room # NN-10, The Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH 44195, USA.
authors.forename: Santanu
authors.initials: S
authors.lastname: Bose
authors.affiliation: Department of Virology, Lerner Research Institute, Room # NN-10, The Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH 44195, USA.
authors.forename: Manjula
authors.initials: M
authors.lastname: Mathur
authors.affiliation: Department of Virology, Lerner Research Institute, Room # NN-10, The Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH 44195, USA.
authors.forename: Patricia
authors.initials: P
authors.lastname: Bates
authors.affiliation: Department of Virology, Lerner Research Institute, Room # NN-10, The Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH 44195, USA.
authors.forename: Nikita
authors.initials: N
authors.lastname: Joshi
authors.affiliation: Department of Virology, Lerner Research Institute, Room # NN-10, The Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH 44195, USA.
authors.forename: Amiya K
authors.initials: AK
authors.lastname: Banerjee
mesh_terms: D000818:Animals; D002460:Cell Line; D006224:Cricetinae; D021984:Cyclophilin A / Q000037:antagonists & inhibitors / Q000378:metabolism*; D016572:Cyclosporine / Q000494:pharmacology; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D019251:Nucleocapsid / Q000378:metabolism; D019590:Nucleocapsid Proteins; D012703:Serotyping; D014721:Vesicular stomatitis Indiana virus / Q000145:classification / Q000502:physiology*; D018116:Vesiculovirus; D014771:Virion / Q000378:metabolism; D014779:Virus Replication
chemical_list: D019590:Nucleocapsid Proteins; C105951:SDZ 211-811; D016572:Cyclosporine; D021984:Cyclophilin A