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

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          Abstract

          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.

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          Author and article information

          Journal
          Microbiol. Immunol.
          Microbiology and immunology
          Wiley-Blackwell
          1348-0421
          0385-5600
          May 02 2017
          Affiliations
          [1 ] Department of Infectious Diseases, Kobe Institute of Health, 4-6-5, Minatojima-Nakamachi, Chuo-ku, Kobe 650-0046, Japan.
          [2 ] Thermocell Inc, Shinagawa-ku, Tokyo 141-0022, Japan.
          [3 ] Department of International Health, Kobe University Graduate School of Health Sciences, Suma-ku, Kobe 615-0124, Japan.
          [4 ] Medical Genetics Research Center, Nara Medical University, Kashihara, Nara 634-8521, Japan.
          [5 ] Department of Virology 1, National Institute of Infectious Diseases, Toyama, Shinjuku, Tokyo 162-8640, Japan.
          [6 ] Divison of Protein Regulation Research, Medical Research Institute, Kanazawa Medical University, Ishikawa 920-0293, Japan.
          [7 ] Division of Molecular Oncology and Virology, Medical Research Institute, Kanazawa Medical University, Ishikawa 920-0293, Japan.
          Article
          10.1111/1348-0421.12486
          28463406
          a2690759-1391-48be-a700-b93cd0365491
          History

          CPT11,IMR-32,JC,JCI,polyomavirus
          CPT11, IMR-32, JC, JCI, polyomavirus

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