title: Suppressive effect of topoisomerase inhibitors on JC polyomavirus propagation in human neuroblastoma cells.
abstract: 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 β-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 β-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 β-lapachone affects JCPyV propagation in human neuroblastoma cell lines, suggesting that topotecan and β-lapachone could potentially be used to treat PML.
authors.affiliation: Department of Infectious Diseases, Kobe Institute of Health, 4-6-5, Minatojima-Nakamachi, Chuo-ku, Kobe 650-0046.
authors.forename: Souichi
authors.initials: S
authors.lastname: Nukuzuma
authors.affiliation: Department of Virology 1, National Institute of Infectious Diseases, Toyama, Shinjuku, Tokyo 162-8640.
authors.forename: Kazuo
authors.initials: K
authors.lastname: Nakamichi
authors.affiliation: Department of International Health, Kobe University Graduate School of Health Sciences, Suma-ku, Kobe 615-0124.
authors.forename: Masanori
authors.initials: M
authors.lastname: Kameoka
authors.affiliation: Medical Genetics Research Center, Nara Medical University, Kashihara, Nara 634-8521.
authors.forename: Shigeki
authors.initials: S
authors.lastname: Sugiura
authors.affiliation: Soara Medical, Shinagawa-ku, Tokyo 141-0022.
authors.forename: Chiyoko
authors.initials: C
authors.lastname: Nukuzuma
authors.affiliation: Divison of Protein Regulation Research, Medical Research Institute, Kanazawa Medical University, Ishikawa 920-0293.
authors.forename: Takafumi
authors.initials: T
authors.lastname: Tasaki
authors.affiliation: Division of Molecular Oncology and Virology, Medical Research Institute, Kanazawa Medical University, Ishikawa 920-0293, Japan.
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Takegami
mesh_terms: D000998:Antiviral Agents / Q000494:pharmacology; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D004261:DNA Replication / Q000187:drug effects; D004279:DNA, Viral / Q000235:genetics; D006801:Humans; D007577:JC Virus / Q000187:drug effects* / Q000235:genetics / Q000502:physiology*; D007968:Leukoencephalopathy, Progressive Multifocal / Q000188:drug therapy* / Q000821:virology*; D009285:Naphthoquinones / Q000494:pharmacology; D009447:Neuroblastoma / Q000821:virology*; D059004:Topoisomerase I Inhibitors / Q000494:pharmacology; D059003:Topoisomerase Inhibitors / Q000494:pharmacology*; D019772:Topotecan / Q000494:pharmacology; D014779:Virus Replication / Q000187:drug effects
chemical_list: D000998:Antiviral Agents; D004279:DNA, Viral; D009285:Naphthoquinones; D059004:Topoisomerase I Inhibitors; D059003:Topoisomerase Inhibitors; C014638:beta-lapachone; D019772:Topotecan
keywords: IMR-32; JC polyomavirus; JCI; topotecan; β-lapachone