4.2 Article

Suppressive effect of topoisomerase inhibitors on JC polyomavirus propagation in human neuroblastoma cells

期刊

MICROBIOLOGY AND IMMUNOLOGY
卷 60, 期 4, 页码 253-260

出版社

WILEY-BLACKWELL
DOI: 10.1111/1348-0421.12372

关键词

-lapachone; IMR-32; JCI; JC polyomavirus; topotecan

资金

  1. Research Committee of Prion Disease and Slow Virus Infection
  2. Ministry of Health, Labor and Welfare of Japan
  3. High-Tech Center of Kanazawa Medical University [H2011-10]
  4. JSPS [26461286]
  5. Grants-in-Aid for Scientific Research [25430119, 26461286] Funding Source: KAKEN

向作者/读者索取更多资源

JC polyomavirus (JCPyV) causes progressive multifocal leukoencephalopathy (PML), a fatal demyelinating disease of the central nervous system, in immunocompromised patients. Because no drugs have been approved for treating PML, many antiviral agents are currently being investigated for this purpose. The inhibitory effects of the topoisomerase I inhibitors topotecan and -lapachone were assessed by investigating viral replication, propagation and viral protein 1 (VP1) production in cultured cells. JCPyV replication was assayed using the human neuroblastoma cell line IMR-32 transfected with the JCPyV plasmid and RT- PCR combined with Dpn I treatment. Dpn I digests the input plasmid DNA containing methylated adenosine, but not newly replicated JCPyV DNA, in IMR-32 cells. It was found that JCPyV replicates less in IMR-32 cells treated with topotecan or -lapachone than in untreated cells. Moreover, drug treatment of JCI cells, which are IMR-32 cells persistently infected with JCPyV, led to a reduction in the amount of JCPyV DNA and population of VP1-positive cells. These results demonstrate that topotecan and -lapachone affects JCPyV propagation in human neuroblastoma cell lines, suggesting that topotecan and -lapachone could potentially be used to treat PML.

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