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Molecular characterization of a JC virus (Sap-1) clone derived from a cerebellar form of progressive multifocal leukoencephalopathy

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Summary

Progressive multifocal leukoencephalopathy (PML) is a demyelinating disease caused by polyomavirus JC (JCV). In the majority of cases of PML the cerebrum is mainly affected (cerebral PML) but on rare occasions lesions are restricted to the cerebellum and brain stem (cerebellar PML). We report a rare cerebellar PML case which occurred in a Japanese patient undergoing prolonged hemodialysis treatment. To understand the molecular basis of the viral tissue tropism, we molecularly cloned JCV DNA and compared it with those of cerebral PML. Of ten clones analyzed nine showed identical fragment patterns after digestion with various restriction endonucleases, and we designated these clones Sap-1. It could be shown that the basic structures of the regulatory regions are similar between Sap-1 and isolates from cerebral PML. Restriction endonuclease mapping analysis was used to examine the genetic relationship between Sap-1 and urine-derived isolates containing the archetypal regulatory sequence. We found that Sap-1 was genetically related to an archetypal JCV isolate in Japan.

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References

  1. Chuke W-F, Walker DL, Peitzman LB, Frisque RJ (1986) Construction and characterization of hybrid polyomavirus genomes. J Virol 60:960–971

    Google Scholar 

  2. Doerries K (1984) Progressive multifocal leukoencephalopathy analysis of JC virus DNA from brain and kidney tissue. Virus Res 1:25–38

    Google Scholar 

  3. Dower WJ, Miller JF, Ragsdale CW (1988) High efficiency transformation of E. coli by high voltage electroporation. Nucleic Acid Res 16:6127–6145

    Google Scholar 

  4. Feinberg AP, Vogelstein B (1984) Addendum: a technique for radiolabeling DNA restriction endonuclease fragments to high specific activity. Anal Biochem 137:266–267

    Google Scholar 

  5. Frisque RJ, Bream GL, Cannella MT (1984) Human polyomavirus JC virus genome. J Virol 51:458–469

    Google Scholar 

  6. Furuta Y, Shinohara T, Sano K, Meguro M, Nagashima K (1990) In situ hybridisation with digoxigenin labelled DNA probes for detection of viral genomes. J Clin Pathol 43:806–809

    Google Scholar 

  7. Hsu SM, Raine L, Fanger H (1981) Use of avidin-biotinperoxidase complex (ABC) in immunoperoxidase techniques: a comparison between ABC and unlabeled antibody (PAP) procedures. J Histochem Cytochem 20:577–580

    Google Scholar 

  8. Jones HR, Hedley-Whyte ET, Freidberg SR, Kellecher JE, Krolikowski J (1982) Primary cerebellopontine progressive mutifocal leukoencephalopathy diagnosed premortem by cerebellar biopsy. Ann Neurol 11:199–202

    Google Scholar 

  9. Kenny S, Natarajan V, Strike D, Khoury G, Salzman NP (1984) JC virus enhancer-promoter active in human brain cells. Science 226:1337–1339

    Google Scholar 

  10. Khalili K, Rappaport J, Khoury G (1988) Nuclear factors in human brain cells bind specifically to the JCV regulatory region. EMBO J 7:1205–1210

    Google Scholar 

  11. Loeber G, Doerries K (1988) DNA rearrangement in organspecific variants of polyomavirus JC strain: GS. J Virol 62:1730–1735

    Google Scholar 

  12. Martin JD, King DM, Slauch JM, Frisque RJ (1985) Differences in regulatory sequences of naturally occurring JC virus variants. J Virol 53:306–311

    Google Scholar 

  13. Matsubara O, Nakagawa S, Shinoda T Iwamoto H, Kanno J, Okeda R, Kasuga T (1984) Progressive multifocal leukoencephalopathy associated with prolonged hemodialysis treatment. Virchows Arch [A] 403:301–305

    Google Scholar 

  14. Matsuda M, Jona M, Yasui K, Nagashima K (1987) Genetic characterization of JC virus Tokyo-1 strain, a variant oncogenic in rodents. Virus Res 7:159–168

    Google Scholar 

  15. Nagashima K, Yamaguchi K, Yasui K, Ogiwara H (1981) Progressive multifocal leukoencephalopathy. Neuropathology and virus isolation. Acta Pathol Jpn 31:953–961

    Google Scholar 

  16. Nagashima K, Yasui K, Kimura J, Washizu M, Yamaguchi K, Mori W (1984) Induction of brain tumors by a newly isolated JC virus (Tokyo-1). Am J Pathol 116:455–463

    Google Scholar 

  17. Padgett BL, Walker DL, ZuRhein GM, Eckroade RJ, Dessel BH (1971) Cultivation of papova-like virus from human brain with progressive multifocal leukoencephalopathy. Lancet I:1257–1260

    Google Scholar 

  18. Parr J, Horoupian DS, Winkelman C (1979). Cerebellar form of progressive multifocal leukoencephalopathy (PML). Can J Neurol Sci 6:123–128

    Google Scholar 

  19. Rockwell D, Rubin FL, Winkelstein A Mendelow H (1976) Absence of immune deficiencies in a case of progressive multifocal leukoencephalopathy. Am J Med 61:433–436

    Google Scholar 

  20. Sambrook J, Fritsch EF, Maniatis T (1989) Molecular cloning. A laboratory manual, 2nd edn. Cold Spring Harbor Laboratory Press, Cold Spring Harbor

    Google Scholar 

  21. Sanger F, Nicklen S, Coulson AR (1977) DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci USA 74:5463–5467

    Google Scholar 

  22. Walker DL (1985) Progressive multifocal leukoencephalopathy. Handb Clin Neurol 47:503–524

    Google Scholar 

  23. Yogo Y, Kitamura T, Sugimoto C, Ueki T, Asao Y, Hara K, Taguchi F (1990) Isolation of a possible archetypal JC virus DNA sequence from nonimmunocompromised individuals. J Virol 64:3139–3143

    Google Scholar 

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Supported by the Suhara Memorial Foundation (Sapporo), and a Special Grant-in-Aid for Promotion of Education and Science in Hokkaido University, provided by the Ministry of Education, Science and Culture. K. Nagashima is supported by a Grant-in-Aid from the Ministry of Education, Science and Culture, Japan, No. 02807036

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Takahashi, H., Yogo, Y., Furuta, Y. et al. Molecular characterization of a JC virus (Sap-1) clone derived from a cerebellar form of progressive multifocal leukoencephalopathy. Acta Neuropathol 83, 105–112 (1992). https://doi.org/10.1007/BF00308469

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  • DOI: https://doi.org/10.1007/BF00308469

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