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. 1996 Mar;70(3):1512–1520. doi: 10.1128/jvi.70.3.1512-1520.1996

Functional comparison of PML-type and archetype strains of JC virus.

E Sock 1, K Renner 1, D Feist 1, H Leger 1, M Wegner 1
PMCID: PMC189972  PMID: 8627669

Abstract

Isolates of the human polyomavirus JC can be grouped as either PML-type or archetype strains primarily on the basis of divergence in their regulatory regions. Only PML-type viruses have so far been found to be associated with the human demyelinating disease progressive multifocal leukoencephalopathy. Here we have compared the functional properties of archetype and PML-type regulatory regions with regard to DNA replication and viral gene expression. No significant differences could be detected between archetype and PML-type regions in their ability to direct episomal DNA replication in the presence of JC virus T antigen. When viral gene expression was examined, early- and late-gene promoters from all PML-type strains exhibited a significantly higher activity in glial than in nonglial cells. Surprisingly, archetype strain promoters were also preferentially active in glial cells, although this effect was less pronounced than in PML-type strains. Furthermore, all promoters from archetype strains reacted to the presence of viral T antigen or the glial transcription factor Tst-1/Oct6 in a manner similar to the promoters of the PML-type viral strain Mad-1. Interestingly, T antigen and Tst-1/Oct6 were found to function in a species-specific and cell-type-specific manner, respectively. We concluded from our experiments that the differences in the regulatory regions cannot account for the different biology of archetype and PML-type viral strains.

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Selected References

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  1. Alwine J. C., Reed S. I., Stark G. R. Characterization of the autoregulation of simian virus 40 gene A. J Virol. 1977 Oct;24(1):22–27. doi: 10.1128/jvi.24.1.22-27.1977. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Amemiya K., Traub R., Durham L., Major E. O. Adjacent nuclear factor-1 and activator protein binding sites in the enhancer of the neurotropic JC virus. A common characteristic of many brain-specific genes. J Biol Chem. 1992 Jul 15;267(20):14204–14211. [PubMed] [Google Scholar]
  3. Amemiya K., Traub R., Durham L., Major E. O. Interaction of a nuclear factor-1-like protein with the regulatory region of the human polyomavirus JC virus. J Biol Chem. 1989 Apr 25;264(12):7025–7032. [PubMed] [Google Scholar]
  4. Atwood W. J., Wang L., Durham L. C., Amemiya K., Traub R. G., Major E. O. Evaluation of the role of cytokine activation in the multiplication of JC virus (JCV) in human fetal glial cells. J Neurovirol. 1995 Mar;1(1):40–49. doi: 10.3109/13550289509111009. [DOI] [PubMed] [Google Scholar]
  5. Ault G. S., Stoner G. L. Human polyomavirus JC promoter/enhancer rearrangement patterns from progressive multifocal leukoencephalopathy brain are unique derivatives of a single archetypal structure. J Gen Virol. 1993 Aug;74(Pt 8):1499–1507. doi: 10.1099/0022-1317-74-8-1499. [DOI] [PubMed] [Google Scholar]
  6. Berger J. R., Kaszovitz B., Post M. J., Dickinson G. Progressive multifocal leukoencephalopathy associated with human immunodeficiency virus infection. A review of the literature with a report of sixteen cases. Ann Intern Med. 1987 Jul;107(1):78–87. doi: 10.7326/0003-4819-107-1-78. [DOI] [PubMed] [Google Scholar]
  7. Brady J., Bolen J. B., Radonovich M., Salzman N., Khoury G. Stimulation of simian virus 40 late gene expression by simian virus 40 tumor antigen. Proc Natl Acad Sci U S A. 1984 Apr;81(7):2040–2044. doi: 10.1073/pnas.81.7.2040. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Chen C., Okayama H. High-efficiency transformation of mammalian cells by plasmid DNA. Mol Cell Biol. 1987 Aug;7(8):2745–2752. doi: 10.1128/mcb.7.8.2745. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Collarini E. J., Kuhn R., Marshall C. J., Monuki E. S., Lemke G., Richardson W. D. Down-regulation of the POU transcription factor SCIP is an early event in oligodendrocyte differentiation in vitro. Development. 1992 Sep;116(1):193–200. doi: 10.1242/dev.116.1.193. [DOI] [PubMed] [Google Scholar]
  10. DeLucia A. L., Deb S., Partin K., Tegtmeyer P. Functional interactions of the simian virus 40 core origin of replication with flanking regulatory sequences. J Virol. 1986 Jan;57(1):138–144. doi: 10.1128/jvi.57.1.138-144.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. DiMaio D., Nathans D. Regulatory mutants of simian virus 40. Effect of mutations at a T antigen binding site on DNA replication and expression of viral genes. J Mol Biol. 1982 Apr 15;156(3):531–548. doi: 10.1016/0022-2836(82)90265-0. [DOI] [PubMed] [Google Scholar]
  12. Fanning E. Simian virus 40 large T antigen: the puzzle, the pieces, and the emerging picture. J Virol. 1992 Mar;66(3):1289–1293. doi: 10.1128/jvi.66.3.1289-1293.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Feigenbaum L., Khalili K., Major E., Khoury G. Regulation of the host range of human papovavirus JCV. Proc Natl Acad Sci U S A. 1987 Jun;84(11):3695–3698. doi: 10.1073/pnas.84.11.3695. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Flaegstad T., Sundsfjord A., Arthur R. R., Pedersen M., Traavik T., Subramani S. Amplification and sequencing of the control regions of BK and JC virus from human urine by polymerase chain reaction. Virology. 1991 Feb;180(2):553–560. doi: 10.1016/0042-6822(91)90069-n. [DOI] [PubMed] [Google Scholar]
  15. Frisque R. J., Bream G. L., Cannella M. T. Human polyomavirus JC virus genome. J Virol. 1984 Aug;51(2):458–469. doi: 10.1128/jvi.51.2.458-469.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Guo Z. S., Gutierrez C., Heine U., Sogo J. M., Depamphilis M. L. Origin auxiliary sequences can facilitate initiation of simian virus 40 DNA replication in vitro as they do in vivo. Mol Cell Biol. 1989 Sep;9(9):3593–3602. doi: 10.1128/mcb.9.9.3593. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Hansen U., Tenen D. G., Livingston D. M., Sharp P. A. T antigen repression of SV40 early transcription from two promoters. Cell. 1981 Dec;27(3 Pt 2):603–613. doi: 10.1016/0092-8674(81)90402-5. [DOI] [PubMed] [Google Scholar]
  18. He X., Gerrero R., Simmons D. M., Park R. E., Lin C. J., Swanson L. W., Rosenfeld M. G. Tst-1, a member of the POU domain gene family, binds the promoter of the gene encoding the cell surface adhesion molecule P0. Mol Cell Biol. 1991 Mar;11(3):1739–1744. doi: 10.1128/mcb.11.3.1739. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Henson J. W. Regulation of the glial-specific JC virus early promoter by the transcription factor Sp1. J Biol Chem. 1994 Jan 14;269(2):1046–1050. [PubMed] [Google Scholar]
  20. Henson J. W., Schnitker B. L., Lee T. S., McAllister J. Cell-specific activation of the glial-specific JC virus early promoter by large T antigen. J Biol Chem. 1995 Jun 2;270(22):13240–13245. doi: 10.1074/jbc.270.22.13240. [DOI] [PubMed] [Google Scholar]
  21. Hertz G. Z., Mertz J. E. Bidirectional promoter elements of simian virus 40 are required for efficient replication of the viral DNA. Mol Cell Biol. 1986 Oct;6(10):3513–3522. doi: 10.1128/mcb.6.10.3513. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Iida T., Kitamura T., Guo J., Taguchi F., Aso Y., Nagashima K., Yogo Y. Origin of JC polyomavirus variants associated with progressive multifocal leukoencephalopathy. Proc Natl Acad Sci U S A. 1993 Jun 1;90(11):5062–5065. doi: 10.1073/pnas.90.11.5062. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Keller J. M., Alwine J. C. Activation of the SV40 late promoter: direct effects of T antigen in the absence of viral DNA replication. Cell. 1984 Feb;36(2):381–389. doi: 10.1016/0092-8674(84)90231-9. [DOI] [PubMed] [Google Scholar]
  24. Kenney S., Natarajan V., Strike D., Khoury G., Salzman N. P. JC virus enhancer-promoter active in human brain cells. Science. 1984 Dec 14;226(4680):1337–1339. doi: 10.1126/science.6095453. [DOI] [PubMed] [Google Scholar]
  25. Khoury G., May E. Regulation of early and late simian virus 40 transcription: overproduction of early viral RNA in the absence of a functional T-antigen. J Virol. 1977 Jul;23(1):167–176. doi: 10.1128/jvi.23.1.167-176.1977. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Krebs C. J., McAvoy M. T., Kumar G. The JC virus minimal core promoter is glial cell specific in vivo. J Virol. 1995 Apr;69(4):2434–2442. doi: 10.1128/jvi.69.4.2434-2442.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Kuhn R., Monuki E. S., Lemke G. The gene encoding the transcription factor SCIP has features of an expressed retroposon. Mol Cell Biol. 1991 Sep;11(9):4642–4650. doi: 10.1128/mcb.11.9.4642. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Lashgari M. S., Tada H., Amini S., Khalili K. Regulation of JCVL promoter function: transactivation of JCVL promoter by JCV and SV40 early proteins. Virology. 1989 May;170(1):292–295. doi: 10.1016/0042-6822(89)90381-4. [DOI] [PubMed] [Google Scholar]
  29. Lee-Chen G. J., Woodworth-Gutai M. Simian virus 40 DNA replication: functional organization of regulatory elements. Mol Cell Biol. 1986 Sep;6(9):3086–3093. doi: 10.1128/mcb.6.9.3086. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Li J. J., Peden K. W., Dixon R. A., Kelly T. Functional organization of the simian virus 40 origin of DNA replication. Mol Cell Biol. 1986 Apr;6(4):1117–1128. doi: 10.1128/mcb.6.4.1117. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Loeber G., Dörries K. DNA rearrangements in organ-specific variants of polyomavirus JC strain GS. J Virol. 1988 May;62(5):1730–1735. doi: 10.1128/jvi.62.5.1730-1735.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Lynch K. J., Frisque R. J. Factors contributing to the restricted DNA replicating activity of JC virus. Virology. 1991 Jan;180(1):306–317. doi: 10.1016/0042-6822(91)90035-a. [DOI] [PubMed] [Google Scholar]
  33. Lynch K. J., Frisque R. J. Identification of critical elements within the JC virus DNA replication origin. J Virol. 1990 Dec;64(12):5812–5822. doi: 10.1128/jvi.64.12.5812-5822.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Major E. O., Amemiya K., Tornatore C. S., Houff S. A., Berger J. R. Pathogenesis and molecular biology of progressive multifocal leukoencephalopathy, the JC virus-induced demyelinating disease of the human brain. Clin Microbiol Rev. 1992 Jan;5(1):49–73. doi: 10.1128/cmr.5.1.49. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Major E. O., Miller A. E., Mourrain P., Traub R. G., de Widt E., Sever J. Establishment of a line of human fetal glial cells that supports JC virus multiplication. Proc Natl Acad Sci U S A. 1985 Feb;82(4):1257–1261. doi: 10.1073/pnas.82.4.1257. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Mandl C., Walker D. L., Frisque R. J. Derivation and characterization of POJ cells, transformed human fetal glial cells that retain their permissivity for JC virus. J Virol. 1987 Mar;61(3):755–763. doi: 10.1128/jvi.61.3.755-763.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Markowitz R. B., Eaton B. A., Kubik M. F., Latorra D., McGregor J. A., Dynan W. S. BK virus and JC virus shed during pregnancy have predominantly archetypal regulatory regions. J Virol. 1991 Aug;65(8):4515–4519. doi: 10.1128/jvi.65.8.4515-4519.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Martin J. D., King D. M., Slauch J. M., Frisque R. J. Differences in regulatory sequences of naturally occurring JC virus variants. J Virol. 1985 Jan;53(1):306–311. doi: 10.1128/jvi.53.1.306-311.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. McKnight S., Tjian R. Transcriptional selectivity of viral genes in mammalian cells. Cell. 1986 Sep 12;46(6):795–805. doi: 10.1016/0092-8674(86)90061-9. [DOI] [PubMed] [Google Scholar]
  40. Meijer D., Graus A., Kraay R., Langeveld A., Mulder M. P., Grosveld G. The octamer binding factor Oct6: cDNA cloning and expression in early embryonic cells. Nucleic Acids Res. 1990 Dec 25;18(24):7357–7365. doi: 10.1093/nar/18.24.7357. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Monuki E. S., Kuhn R., Lemke G. Cell-specific action and mutable structure of a transcription factor effector domain. Proc Natl Acad Sci U S A. 1993 Nov 1;90(21):9978–9982. doi: 10.1073/pnas.90.21.9978. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Monuki E. S., Kuhn R., Lemke G. Repression of the myelin P0 gene by the POU transcription factor SCIP. Mech Dev. 1993 Jul;42(1-2):15–32. doi: 10.1016/0925-4773(93)90095-f. [DOI] [PubMed] [Google Scholar]
  43. Monuki E. S., Weinmaster G., Kuhn R., Lemke G. SCIP: a glial POU domain gene regulated by cyclic AMP. Neuron. 1989 Dec;3(6):783–793. doi: 10.1016/0896-6273(89)90247-x. [DOI] [PubMed] [Google Scholar]
  44. Myers R. M., Rio D. C., Robbins A. K., Tjian R. SV40 gene expression is modulated by the cooperative binding of T antigen to DNA. Cell. 1981 Aug;25(2):373–384. doi: 10.1016/0092-8674(81)90056-8. [DOI] [PubMed] [Google Scholar]
  45. Nakshatri H., Pater A., Pater M. M. Activity and enhancer binding factors for JC virus regulatory elements in differentiating embryonal carcinoma cells. Virology. 1990 Aug;177(2):784–789. doi: 10.1016/0042-6822(90)90550-b. [DOI] [PubMed] [Google Scholar]
  46. Padgett B. L., Walker D. L. Prevalence of antibodies in human sera against JC virus, an isolate from a case of progressive multifocal leukoencephalopathy. J Infect Dis. 1973 Apr;127(4):467–470. doi: 10.1093/infdis/127.4.467. [DOI] [PubMed] [Google Scholar]
  47. Ranganathan P. N., Khalili K. The transcriptional enhancer element, kappa B, regulates promoter activity of the human neurotropic virus, JCV, in cells derived from the CNS. Nucleic Acids Res. 1993 Apr 25;21(8):1959–1964. doi: 10.1093/nar/21.8.1959. [DOI] [PMC free article] [PubMed] [Google Scholar]
  48. Renner K., Leger H., Wegner M. The POU domain protein Tst-1 and papovaviral large tumor antigen function synergistically to stimulate glia-specific gene expression of JC virus. Proc Natl Acad Sci U S A. 1994 Jul 5;91(14):6433–6437. doi: 10.1073/pnas.91.14.6433. [DOI] [PMC free article] [PubMed] [Google Scholar]
  49. Rio D., Robbins A., Myers R., Tjian R. Regulation of simian virus 40 early transcription in vitro by a purified tumor antigen. Proc Natl Acad Sci U S A. 1980 Oct;77(10):5706–5710. doi: 10.1073/pnas.77.10.5706. [DOI] [PMC free article] [PubMed] [Google Scholar]
  50. Schreiber E., Matthias P., Müller M. M., Schaffner W. Rapid detection of octamer binding proteins with 'mini-extracts', prepared from a small number of cells. Nucleic Acids Res. 1989 Aug 11;17(15):6419–6419. doi: 10.1093/nar/17.15.6419. [DOI] [PMC free article] [PubMed] [Google Scholar]
  51. Sock E., Wegner M., Fortunato E. A., Grummt F. Large T-antigen and sequences within the regulatory region of JC virus both contribute to the features of JC virus DNA replication. Virology. 1993 Dec;197(2):537–548. doi: 10.1006/viro.1993.1627. [DOI] [PubMed] [Google Scholar]
  52. Sock E., Wegner M., Grummt F. DNA replication of human polyomavirus JC is stimulated by NF-I in vivo. Virology. 1991 May;182(1):298–308. doi: 10.1016/0042-6822(91)90673-y. [DOI] [PubMed] [Google Scholar]
  53. Stoner G. L., Ryschkewitsch C. F., Walker D. L., Webster H. D. JC papovavirus large tumor (T)-antigen expression in brain tissue of acquired immune deficiency syndrome (AIDS) and non-AIDS patients with progressive multifocal leukoencephalopathy. Proc Natl Acad Sci U S A. 1986 Apr;83(7):2271–2275. doi: 10.1073/pnas.83.7.2271. [DOI] [PMC free article] [PubMed] [Google Scholar]
  54. Suzuki N., Rohdewohld H., Neuman T., Gruss P., Schöler H. R. Oct-6: a POU transcription factor expressed in embryonal stem cells and in the developing brain. EMBO J. 1990 Nov;9(11):3723–3732. doi: 10.1002/j.1460-2075.1990.tb07585.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  55. Tada H., Lashgari M., Rappaport J., Khalili K. Cell type-specific expression of JC virus early promoter is determined by positive and negative regulation. J Virol. 1989 Jan;63(1):463–466. doi: 10.1128/jvi.63.1.463-466.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  56. Tamura T., Inoue T., Nagata K., Mikoshiba K. Enhancer of human polyoma JC virus contains nuclear factor I-binding sequences; analysis using mouse brain nuclear extracts. Biochem Biophys Res Commun. 1988 Dec 15;157(2):419–425. doi: 10.1016/s0006-291x(88)80265-1. [DOI] [PubMed] [Google Scholar]
  57. Tominaga T., Yogo Y., Kitamura T., Aso Y. Persistence of archetypal JC virus DNA in normal renal tissue derived from tumor-bearing patients. Virology. 1992 Feb;186(2):736–741. doi: 10.1016/0042-6822(92)90040-v. [DOI] [PubMed] [Google Scholar]
  58. Weber T., Turner R. W., Frye S., Ruf B., Haas J., Schielke E., Pohle H. D., Lüke W., Lüer W., Felgenhauer K. Specific diagnosis of progressive multifocal leukoencephalopathy by polymerase chain reaction. J Infect Dis. 1994 May;169(5):1138–1141. doi: 10.1093/infdis/169.5.1138. [DOI] [PubMed] [Google Scholar]
  59. Wegner M., Drolet D. W., Rosenfeld M. G. Regulation of JC virus by the POU-domain transcription factor Tst-1: implications for progressive multifocal leukoencephalopathy. Proc Natl Acad Sci U S A. 1993 May 15;90(10):4743–4747. doi: 10.1073/pnas.90.10.4743. [DOI] [PMC free article] [PubMed] [Google Scholar]
  60. White F. A., 3rd, Ishaq M., Stoner G. L., Frisque R. J. JC virus DNA is present in many human brain samples from patients without progressive multifocal leukoencephalopathy. J Virol. 1992 Oct;66(10):5726–5734. doi: 10.1128/jvi.66.10.5726-5734.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  61. Yogo Y., Iida T., Taguchi F., Kitamura T., Aso Y. Typing of human polyomavirus JC virus on the basis of restriction fragment length polymorphisms. J Clin Microbiol. 1991 Oct;29(10):2130–2138. doi: 10.1128/jcm.29.10.2130-2138.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  62. Yogo Y., Kitamura T., Sugimoto C., Ueki T., Aso Y., Hara K., Taguchi F. Isolation of a possible archetypal JC virus DNA sequence from nonimmunocompromised individuals. J Virol. 1990 Jun;64(6):3139–3143. doi: 10.1128/jvi.64.6.3139-3143.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]

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