Cyclophilins are peptidyl prolyl cis-trans isomerases that are highly conserved throughout eukaryotes and are best known for being the cellular target of the immunosuppressive drug cyclosporin A (CsA). The activity of CsA is caused by the drug forming a complex with cyclophilin A and inhibiting the calmodulin-dependent phosphoprotein phosphatase calcineurin. We cloned the cpcypl, a hypovirus negatively regulated cyclophilin-encoding gene in the phytopathogenic fungus Cryphonectria parasitica and investigated its function by deletion of cpcyp1. The wild type C. parasitica strain EP155 was sensitive to CsA butâ–³cpcyp1 was not, demonstrating that CPCYP1 was the target of CsA. Deletion of cpcyp1 resulted in reduced growth, reduced aerial hyphae and enhenced orange gigment for theâ–³cpcyp1 mutant. More importantly, the null mutant show a reduced virulence when it was inculated to Chinese chestnut stems as compared to the wild-type strain EP155. These data implicate that CPCYP1 may be a virulenc factor in C. parasitica...
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