Requirement for cyclophilin A for the replication of vesicular stomatitis virus New Jersey serotype.
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.
Bose
Santanu
S
Department of Virology, Lerner Research Institute, Room # NN-10, The Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH 44195, USA.
Mathur
Manjula
M
Department of Virology, Lerner Research Institute, Room # NN-10, The Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH 44195, USA.
Bates
Patricia
P
Department of Virology, Lerner Research Institute, Room # NN-10, The Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH 44195, USA.
Joshi
Nikita
N
Department of Virology, Lerner Research Institute, Room # NN-10, The Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH 44195, USA.
Banerjee
Amiya K
AK
Department of Virology, Lerner Research Institute, Room # NN-10, The Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH 44195, USA.
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
D019590:Nucleocapsid Proteins; C105951:SDZ 211-811; D016572:Cyclosporine; D021984:Cyclophilin A