Skip to main content
PMC home page
Journal of Virology logoLink to Journal of Virology
. 1996 Apr;70(4):2387–2393. doi: 10.1128/jvi.70.4.2387-2393.1996

Transcription of the JC virus archetype late genome: importance of the kappa B and the 23-base-pair motifs in late promoter activity in glial cells.

R P Mayreddy 1, M Safak 1, M Razmara 1, P Zoltick 1, K Khalili 1
PMCID: PMC190081  PMID: 8642666

Abstract

The transcription control region of the archetype strain of the human polyomavirus JC virus (JCV(Cy)), unlike its neurotropic counterpart (JCV(Mad-1)), contains only one copy of the 98-bp enhancer/promoter repeat with the 23-bp and the 66-bp insertion blocks. Early studies by us and others have indicated that the structural organization of JCV(Mad-1) is critical for glial cell-specific transcription of the viral genome. In addition, the kappa B regulatory motif found in the JCV(Mad-1) genome, which also exists in JCV(Cy), confers inducibility to the JCV(Mad-1) early and late promoters in response to extracellular stimuli. In this study, we have investigated the regulatory role of the 23- and the 66-bp blocks and their functional relationship to the kappa B motif in stimulating transcription of the Cy early and late promoters in glial cells. We demonstrate that mutations in the kappa B motif reduce the basal activity of the Cy early promoter and decrease the levels of its induction by phorbol myristate acetate or factors derived from activated T cells. Under similar circumstances, mutation in the kappa B motif completely abrogated the basal and the induced levels of transcription of the viral late promoter. Using deletion and hybrid promoter constructs, we have demonstrated that the 23-bp block of the Cy promoter plays a critical role in the observed inactivation of Cy late promoter transcription in glial cells. Results from DNA binding studies have indicated the formation of a common nucleoprotein complex with the 23-bp sequence, mutant kappa B (kappa B(mut)), and wild-type kappa B (kappa B(wt)). Analysis of this complex by UV cross-linking has identified a 40-kDa protein which binds to the 23-bp sequence and the kappa B motif. The importance of these findings for the activation of JCV(Cy) under various physiological conditions is discussed.

Full Text

The Full Text of this article is available as a PDF (511.0 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Andrews C. A., Daniel R. W., Shah K. V. Serologic studies of papovavirus infections in pregnant women and renal transplant recipients. Prog Clin Biol Res. 1983;105:133–141. [PubMed] [Google Scholar]
  2. Baeuerle P. A., Henkel T. Function and activation of NF-kappa B in the immune system. Annu Rev Immunol. 1994;12:141–179. doi: 10.1146/annurev.iy.12.040194.001041. [DOI] [PubMed] [Google Scholar]
  3. Berger J. R., Concha M. Progressive multifocal leukoencephalopathy: the evolution of a disease once considered rare. J Neurovirol. 1995 Mar;1(1):5–18. doi: 10.3109/13550289509111006. [DOI] [PubMed] [Google Scholar]
  4. Chesters P. M., Heritage J., McCance D. J. Persistence of DNA sequences of BK virus and JC virus in normal human tissues and in diseased tissues. J Infect Dis. 1983 Apr;147(4):676–684. doi: 10.1093/infdis/147.4.676. [DOI] [PubMed] [Google Scholar]
  5. Coleman D. V., Gardner S. D., Mulholland C., Fridiksdottir V., Porter A. A., Lilford R., Valdimarsson H. Human polyomavirus in pregnancy. A model for the study of defence mechanisms to virus reactivation. Clin Exp Immunol. 1983 Aug;53(2):289–296. [PMC free article] [PubMed] [Google Scholar]
  6. Dörries K. Progressive multifocal leucoencephalopathy: analysis of JC virus DNA from brain and kidney tissue. Virus Res. 1984 Jan;1(1):25–38. doi: 10.1016/0168-1702(84)90032-7. [DOI] [PubMed] [Google Scholar]
  7. 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]
  8. 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]
  9. Gardner S. D., MacKenzie E. F., Smith C., Porter A. A. Prospective study of the human polyomaviruses BK and JC and cytomegalovirus in renal transplant recipients. J Clin Pathol. 1984 May;37(5):578–586. doi: 10.1136/jcp.37.5.578. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Gorman C. M., Moffat L. F., Howard B. H. Recombinant genomes which express chloramphenicol acetyltransferase in mammalian cells. Mol Cell Biol. 1982 Sep;2(9):1044–1051. doi: 10.1128/mcb.2.9.1044. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Graham F. L., van der Eb A. J. A new technique for the assay of infectivity of human adenovirus 5 DNA. Virology. 1973 Apr;52(2):456–467. doi: 10.1016/0042-6822(73)90341-3. [DOI] [PubMed] [Google Scholar]
  12. Grimm S., Baeuerle P. A. The inducible transcription factor NF-kappa B: structure-function relationship of its protein subunits. Biochem J. 1993 Mar 1;290(Pt 2):297–308. doi: 10.1042/bj2900297. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Khalili K., Rappaport J., Khoury G. Nuclear factors in human brain cells bind specifically to the JCV regulatory region. EMBO J. 1988 Apr;7(4):1205–1210. doi: 10.1002/j.1460-2075.1988.tb02932.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Luckow B., Schütz G. CAT constructions with multiple unique restriction sites for the functional analysis of eukaryotic promoters and regulatory elements. Nucleic Acids Res. 1987 Jul 10;15(13):5490–5490. doi: 10.1093/nar/15.13.5490. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. 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]
  16. 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]
  17. 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]
  18. Myers C., Frisque R. J., Arthur R. R. Direct isolation and characterization of JC virus from urine samples of renal and bone marrow transplant patients. J Virol. 1989 Oct;63(10):4445–4449. doi: 10.1128/jvi.63.10.4445-4449.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. RICHARDSON E. P., Jr Progressive multifocal leukoencephalopathy. N Engl J Med. 1961 Oct 26;265:815–823. doi: 10.1056/NEJM196110262651701. [DOI] [PubMed] [Google Scholar]
  20. Raj G. V., Khalili K. Identification and characterization of a novel GGA/C-binding protein, GBP-i, that is rapidly inducible by cytokines. Mol Cell Biol. 1994 Dec;14(12):7770–7781. doi: 10.1128/mcb.14.12.7770. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Raj G. V., Khalili K. Transcriptional regulation: lessons from the human neurotropic polyomavirus, JCV. Virology. 1995 Nov 10;213(2):283–291. doi: 10.1006/viro.1995.0001. [DOI] [PubMed] [Google Scholar]
  22. Rashtchian A., Thornton C. G., Heidecker G. A novel method for site-directed mutagenesis using PCR and uracil DNA glycosylase. PCR Methods Appl. 1992 Nov;2(2):124–130. doi: 10.1101/gr.2.2.124. [DOI] [PubMed] [Google Scholar]
  23. Taylor J. P., Pomerantz R., Bagasra O., Chowdhury M., Rappaport J., Khalili K., Amini S. TAR-independent transactivation by Tat in cells derived from the CNS: a novel mechanism of HIV-1 gene regulation. EMBO J. 1992 Sep;11(9):3395–3403. doi: 10.1002/j.1460-2075.1992.tb05418.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. 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]
  25. Yogo Y., Kitamura T., Sugimoto C., Hara K., Iida T., Taguchi F., Tajima A., Kawabe K., Aso Y. Sequence rearrangement in JC virus DNAs molecularly cloned from immunosuppressed renal transplant patients. J Virol. 1991 May;65(5):2422–2428. doi: 10.1128/jvi.65.5.2422-2428.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. 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]
  27. Zu Rhein G. M. Polyoma-like virions in a human demyelinating disease. Acta Neuropathol. 1967 Mar 6;8(1):57–68. doi: 10.1007/BF00686650. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Virology are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES