CPT11 prevents virus replication in JCI cells persistently infected with JC polyomavirus

JC polyomavirus (JCPyV) is the causative agent of the demyelinating disease in the central nervous system, known as PML in immunocompromised patients. Moreover, PML occurred in patients treated with natalizumab for MS or Crohn's disease as natalizumab-related PML. Many antiviral agents are being investigated due to the lack of drugs currently available for PML. The previous study demonstrated that the topoisomerase I inhibitors topotecan and β-lapachone have inhibitory effects on JCPyV replication in IMR-32 cells. However, both drugs topotecan and β-lapachone show a marginal inhibition of virus propagation in JCI cells using real -time PCR analysis. The inhibitory effect of another topoisomerase I inhibitor, CPT11, was assessed by investigating viral replication, propagation, and VP1 production in cultured cells. JCPyV replication was assayed using real-time PCR combined with Dpn I treatment in IMR-32 cells transfected with JCPyV DNA. It was found that JCPyV replicates less in IMR-32 cells treated with CPT11 than in untreated cells. Moreover, CPT11 treatment of JCI cells persistently infected with JCPyV led to a dose-dependent reduction in the amount of JCPyV DNA and VP1 production. In addition, it was indicated that the inhibitory effect of CPT11 was stronger than that of topotecan and β-lapachone. This study suggests that CPT11 may be a potential anti-JCPyV therapeutic drug for the treatment of PML.