Skip to main content
PMC home page
Journal of Virology logoLink to Journal of Virology
. 1990 Aug;64(8):3864–3871. doi: 10.1128/jvi.64.8.3864-3871.1990

At least two types of control regions can be found among naturally occurring BK virus strains.

A Sundsfjord 1, T Johansen 1, T Flaegstad 1, U Moens 1, P Villand 1, S Subramani 1, T Traavik 1
PMCID: PMC249682  PMID: 2164600

Abstract

The various strains of BK virus (BKV) exhibit a remarkable degree of heterogeneity in the transcriptional control region, which may affect the biological characteristics of a BKV strain. We describe the detection and sequencing of BKV control regions directly from urine samples and after propagation in cell culture. A BKV strain [BKV (TU)] with a control region anatomy not described earlier, as well as a BKV (WW)-like strain [BKV (WWT)], was detected in urine samples by direct sequencing of polymerase chain reaction products. Urine inocula containing BKV (WWT) yielded BKV (TU) upon one passage in cell culture, while BKV (TU) did not change its control region during propagation in cell culture. Analysis of the nucleotide sequence of the transcriptional control regions revealed a partial deletion and duplication in BKV (TU) compared with BKV (WWT). In addition, the control region of BKV (TU) contains two point mutations relative to BKV (WWT). This indicates that both virus strains were probably present in the BKV (WWT)-dominated urine inocula, rather than that BKV (WWT) genomes were rearranged into BKV (TU) genomes during cell propagation. The heterogeneity of the control region of BKV strains is discussed in relation to both confirmed and putative transcription factor-binding sites.

Full text

PDF
3867

Images in this article

3866Image
on p.3866
3868Image
on p.3868

Selected References

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

  1. Apperley J. F., Rice S. J., Bishop J. A., Chia Y. C., Krausz T., Gardner S. D., Goldman J. M. Late-onset hemorrhagic cystitis associated with urinary excretion of polyomaviruses after bone marrow transplantation. Transplantation. 1987 Jan;43(1):108–112. doi: 10.1097/00007890-198701000-00024. [DOI] [PubMed] [Google Scholar]
  2. Arthur R. R., Shah K. V., Baust S. J., Santos G. W., Saral R. Association of BK viruria with hemorrhagic cystitis in recipients of bone marrow transplants. N Engl J Med. 1986 Jul 24;315(4):230–234. doi: 10.1056/NEJM198607243150405. [DOI] [PubMed] [Google Scholar]
  3. Ball R. K., Siegl B., Quellhorst S., Brandner G., Braun D. G. Monoclonal antibodies against simian virus 40 nuclear large T tumour antigen: epitope mapping, papova virus cross-reaction and cell surface staining. EMBO J. 1984 Jul;3(7):1485–1491. doi: 10.1002/j.1460-2075.1984.tb02000.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Berg D. T., Walls J. D., Grinnell B. W. A variant enhancer/regulatory region from a cloned human prototype BK virus genome. Nucleic Acids Res. 1988 Sep 26;16(18):9057–9057. doi: 10.1093/nar/16.18.9057. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Brown P., Tsai T., Gajdusek D. C. Seroepidemiology of human papovaviruses. Discovery of virgin populations and some unusual patterns of antibody prevalence among remote peoples of the world. Am J Epidemiol. 1975 Oct;102(4):331–340. doi: 10.1093/oxfordjournals.aje.a112169. [DOI] [PubMed] [Google Scholar]
  6. Caputo A., Corallini A., Grossi M. P., Carrà L., Balboni P. G., Negrini M., Milanesi G., Federspil G., Barbanti-Brodano G. Episomal DNA of a BK virus variant in a human insulinoma. J Med Virol. 1983;12(1):37–49. doi: 10.1002/jmv.1890120105. [DOI] [PubMed] [Google Scholar]
  7. Cassill J. A., Deyerle K. L., Subramani S. Unidirectional deletion and linker scan analysis of the late promoter of the human papovavirus BK. Virology. 1989 Mar;169(1):172–181. doi: 10.1016/0042-6822(89)90053-6. [DOI] [PubMed] [Google Scholar]
  8. Cassill J. A., Subramani S. The late promoter of the human papovavirus BK is contained within the early promoter enhancer region. Virology. 1988 Sep;166(1):175–185. doi: 10.1016/0042-6822(88)90159-6. [DOI] [PubMed] [Google Scholar]
  9. Chakraborty T., Das G. C. Identification of HeLa cell nuclear factors that bind to and activate the early promoter of human polyomavirus BK in vitro. Mol Cell Biol. 1989 Sep;9(9):3821–3828. doi: 10.1128/mcb.9.9.3821. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Chauhan S., Lecatsas G., Harley E. H. Genome analysis of BK (WW) viral DNA cloned directly from human urine. Intervirology. 1984;22(3):170–176. doi: 10.1159/000149547. [DOI] [PubMed] [Google Scholar]
  11. 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]
  12. Christie K. E., Flaegstad T., Traavik T. Characterization of BK virus-specific antibodies in human sera by Western immunoblotting: use of a zwitterionic detergent for restoring the antibody-binding capacity of electroblotted proteins. J Med Virol. 1988 Feb;24(2):183–190. doi: 10.1002/jmv.1890240207. [DOI] [PubMed] [Google Scholar]
  13. 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]
  14. Coleman D. V., Mackenzie E. F., Gardner S. D., Poulding J. M., Amer B., Russell W. J. Human polyomavirus (BK) infection and ureteric stenosis in renal allograft recipients. J Clin Pathol. 1978 Apr;31(4):338–347. doi: 10.1136/jcp.31.4.338. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Corallini A., Pagnani M., Viadana P., Silini E., Mottes M., Milanesi G., Gerna G., Vettor R., Trapella G., Silvani V. Association of BK virus with human brain tumors and tumors of pancreatic islets. Int J Cancer. 1987 Jan 15;39(1):60–67. doi: 10.1002/ijc.2910390111. [DOI] [PubMed] [Google Scholar]
  16. Dei R., Marmo F., Corte D., Sampietro M. G., Franceschini E., Urbano P. Age-related changes in the prevalence of precipitating antibodies to BK virus in infants and children. J Med Microbiol. 1982 Aug;15(3):285–291. doi: 10.1099/00222615-15-3-285. [DOI] [PubMed] [Google Scholar]
  17. Devereux J., Haeberli P., Smithies O. A comprehensive set of sequence analysis programs for the VAX. Nucleic Acids Res. 1984 Jan 11;12(1 Pt 1):387–395. doi: 10.1093/nar/12.1part1.387. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Deyerle K. L., Cassill J. A., Subramani S. Analysis of the early regulatory region of the human papovavirus BK. Virology. 1987 May;158(1):181–193. doi: 10.1016/0042-6822(87)90252-2. [DOI] [PubMed] [Google Scholar]
  19. Deyerle K. L., Subramani S. Linker scan analysis of the early regulatory region of human papovavirus BK. J Virol. 1988 Sep;62(9):3378–3387. doi: 10.1128/jvi.62.9.3378-3387.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Dörries K., Loeber G., Meixensberger J. Association of polyomaviruses JC, SV40, and BK with human brain tumors. Virology. 1987 Sep;160(1):268–270. doi: 10.1016/0042-6822(87)90071-7. [DOI] [PubMed] [Google Scholar]
  21. Flaegstad T., Traavik T. BK virus in cell culture: infectivity quantitation and sequential expression of antigens detected by immunoperoxidase staining. J Virol Methods. 1987 May;16(1-2):139–146. doi: 10.1016/0166-0934(87)90038-3. [DOI] [PubMed] [Google Scholar]
  22. Flaegstad T., Traavik T., Kolmannskog S., Stokland T. BK virus infection in children with cancer: serological response studied by haemagglutination inhibition, neutralization, and IgG- and IgM-class specific ELISA tests. J Med Virol. 1988 Jan;24(1):33–44. doi: 10.1002/jmv.1890240106. [DOI] [PubMed] [Google Scholar]
  23. Flaegstad T., Traavik T., Kristiansen B. E. Age-dependent prevalence of BK virus IgG and IgM antibodies measured by enzyme-linked immunosorbent assays (ELISA). J Hyg (Lond) 1986 Jun;96(3):523–528. doi: 10.1017/s0022172400066328. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Gardner S. D., Field A. M., Coleman D. V., Hulme B. New human papovavirus (B.K.) isolated from urine after renal transplantation. Lancet. 1971 Jun 19;1(7712):1253–1257. doi: 10.1016/s0140-6736(71)91776-4. [DOI] [PubMed] [Google Scholar]
  25. 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]
  26. Gardner S. D. Prevalence in England of antibody to human polyomavirus (B.k.). Br Med J. 1973 Jan 13;1(5845):77–78. doi: 10.1136/bmj.1.5845.77. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Goudsmit J., Wertheim-van Dillen P., van Strien A., van der Noordaa J. The role of BK virus in acute respiratory tract disease and the presence of BKV DNA in tonsils. J Med Virol. 1982;10(2):91–99. doi: 10.1002/jmv.1890100203. [DOI] [PubMed] [Google Scholar]
  28. Grinnell B. W., Berg D. T., Walls J. D. Negative regulation of the human polyomavirus BK enhancer involves cell-specific interaction with a nuclear repressor. Mol Cell Biol. 1988 Aug;8(8):3448–3457. doi: 10.1128/mcb.8.8.3448. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Grinnell B. W., Berg D. T., Walls J. Activation of the adenovirus and BK virus late promoters: effects of the BK virus enhancer and trans-acting viral early proteins. Mol Cell Biol. 1986 Nov;6(11):3596–3605. doi: 10.1128/mcb.6.11.3596. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Grossi M. P., Caputo A., Meneguzzi G., Corallini A., Carra L., Portolani M., Borgatti M., Milanesi G., Barbanti-Brodano G. Transformation of human embryonic fibroblasts by BK virus, BK virus DNA and a subgenomic BK virus DNA fragment. J Gen Virol. 1982 Dec;63(2):393–403. doi: 10.1099/0022-1317-63-2-393. [DOI] [PubMed] [Google Scholar]
  31. Gyllensten U. B., Erlich H. A. Generation of single-stranded DNA by the polymerase chain reaction and its application to direct sequencing of the HLA-DQA locus. Proc Natl Acad Sci U S A. 1988 Oct;85(20):7652–7656. doi: 10.1073/pnas.85.20.7652. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Harr R., Fällman P., Häggström M., Wahlström L., Gustafsson P. GENEUS, a computer system for DNA and protein sequence analysis containing an information retrieval system for the EMBL data library. Nucleic Acids Res. 1986 Jan 10;14(1):273–284. doi: 10.1093/nar/14.1.273. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Hashida Y., Gaffney P. C., Yunis E. J. Acute hemorrhagic cystitis of childhood and papovavirus-like particles. J Pediatr. 1976 Jul;89(1):85–87. doi: 10.1016/s0022-3476(76)80936-5. [DOI] [PubMed] [Google Scholar]
  34. Heritage J., Chesters P. M., McCance D. J. The persistence of papovavirus BK DNA sequences in normal human renal tissue. J Med Virol. 1981;8(2):143–150. doi: 10.1002/jmv.1890080208. [DOI] [PubMed] [Google Scholar]
  35. Hirt B. Selective extraction of polyoma DNA from infected mouse cell cultures. J Mol Biol. 1967 Jun 14;26(2):365–369. doi: 10.1016/0022-2836(67)90307-5. [DOI] [PubMed] [Google Scholar]
  36. Hogan T. F., Borden E. C., McBain J. A., Padgett B. L., Walker D. L. Human polyomavirus infections with JC virus and BK virus in renal transplant patients. Ann Intern Med. 1980 Mar;92(3):373–378. doi: 10.7326/0003-4819-92-3-373. [DOI] [PubMed] [Google Scholar]
  37. Howley P. M., Mullarkey M. F., Takemoto K. K., Martin M. A. Characterization of human papovavirus BK DNA. J Virol. 1975 Jan;15(1):173–181. doi: 10.1128/jvi.15.1.173-181.1975. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Johansen T., Holm T., Guddal P. H., Sletten K., Haugli F. B., Little C. Cloning and sequencing of the gene encoding the phosphatidylcholine-preferring phospholipase C of Bacillus cereus. Gene. 1988 May 30;65(2):293–304. doi: 10.1016/0378-1119(88)90466-0. [DOI] [PubMed] [Google Scholar]
  39. Jones N. C., Rigby P. W., Ziff E. B. Trans-acting protein factors and the regulation of eukaryotic transcription: lessons from studies on DNA tumor viruses. Genes Dev. 1988 Mar;2(3):267–281. doi: 10.1101/gad.2.3.267. [DOI] [PubMed] [Google Scholar]
  40. Knepper J. E., diMayorca G. Cloning and characterization of BK virus-related DNA sequences from normal and neoplastic human tissues. J Med Virol. 1987 Mar;21(3):289–299. doi: 10.1002/jmv.1890210313. [DOI] [PubMed] [Google Scholar]
  41. Kwok S., Higuchi R. Avoiding false positives with PCR. Nature. 1989 May 18;339(6221):237–238. doi: 10.1038/339237a0. [DOI] [PubMed] [Google Scholar]
  42. 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]
  43. Markowitz R. B., Dynan W. S. Binding of cellular proteins to the regulatory region of BK virus DNA. J Virol. 1988 Sep;62(9):3388–3398. doi: 10.1128/jvi.62.9.3388-3398.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Mew R. T., Lecatsas G., Prozesky O. W., Harley E. H. Characteristics of BK papovavirus DNA prepared directly from human urine. Intervirology. 1981;16(1):14–19. doi: 10.1159/000149242. [DOI] [PubMed] [Google Scholar]
  45. 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]
  46. Myers R. M., Tilly K., Maniatis T. Fine structure genetic analysis of a beta-globin promoter. Science. 1986 May 2;232(4750):613–618. doi: 10.1126/science.3457470. [DOI] [PubMed] [Google Scholar]
  47. Mäntvjärvi R. A. New oncogenic human papovaviruses. Med Biol. 1979 Feb;57(1):29–35. [PubMed] [Google Scholar]
  48. Odenwald W. F., Garbern J., Arnheiter H., Tournier-Lasserve E., Lazzarini R. A. The Hox-1.3 homeo box protein is a sequence-specific DNA-binding phosphoprotein. Genes Dev. 1989 Feb;3(2):158–172. doi: 10.1101/gad.3.2.158. [DOI] [PubMed] [Google Scholar]
  49. Pater A., Pater M. M. Transformation of primary human embryonic kidney cells to anchorage independence by a combination of BK virus DNA and the Harvey-ras oncogene. J Virol. 1986 May;58(2):680–683. doi: 10.1128/jvi.58.2.680-683.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  50. Rosenthal N., Kress M., Gruss P., Khoury G. BK viral enhancer element and a human cellular homolog. Science. 1983 Nov 18;222(4625):749–755. doi: 10.1126/science.6314501. [DOI] [PubMed] [Google Scholar]
  51. Rubinstein R., Pare N., Harley E. H. Structure and function of the transcriptional control region of nonpassaged BK virus. J Virol. 1987 May;61(5):1747–1750. doi: 10.1128/jvi.61.5.1747-1750.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  52. Saiki R. K., Gelfand D. H., Stoffel S., Scharf S. J., Higuchi R., Horn G. T., Mullis K. B., Erlich H. A. Primer-directed enzymatic amplification of DNA with a thermostable DNA polymerase. Science. 1988 Jan 29;239(4839):487–491. doi: 10.1126/science.2448875. [DOI] [PubMed] [Google Scholar]
  53. Seif I., Khoury G., Dhar R. The genome of human papovavirus BKV. Cell. 1979 Dec;18(4):963–977. doi: 10.1016/0092-8674(79)90209-5. [DOI] [PubMed] [Google Scholar]
  54. Shah K. V., Daniel R. W., Warszawski R. M. High prevalence of antibodies to BK virus, an SV40-related papovavirus, in residents of Maryland. J Infect Dis. 1973 Dec;128(6):784–787. doi: 10.1093/infdis/128.6.784. [DOI] [PubMed] [Google Scholar]
  55. Strähle U., Klock G., Schütz G. A DNA sequence of 15 base pairs is sufficient to mediate both glucocorticoid and progesterone induction of gene expression. Proc Natl Acad Sci U S A. 1987 Nov;84(22):7871–7875. doi: 10.1073/pnas.84.22.7871. [DOI] [PMC free article] [PubMed] [Google Scholar]
  56. Sugimoto C., Hara K., Taguchi F., Yogo Y. Growth efficiency of naturally occurring BK virus variants in vivo and in vitro. J Virol. 1989 Jul;63(7):3195–3199. doi: 10.1128/jvi.63.7.3195-3199.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  57. Takemoto K. K., Rabson A. S., Mullarkey M. F., Blaese R. M., Garon C. F., Nelson D. Isolation of papovavirus from brain tumor and urine of a patient with Wiskott-Aldrich syndrome. J Natl Cancer Inst. 1974 Nov;53(5):1205–1207. doi: 10.1093/jnci/53.5.1205. [DOI] [PubMed] [Google Scholar]
  58. Tavis J. E., Walker D. L., Gardner S. D., Frisque R. J. Nucleotide sequence of the human polyomavirus AS virus, an antigenic variant of BK virus. J Virol. 1989 Feb;63(2):901–911. doi: 10.1128/jvi.63.2.901-911.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  59. Watanabe S., Soeda E., Uchida S., Yoshiike K. DNA rearrangement affecting expression of the BK virus transforming gene. J Virol. 1984 Jul;51(1):1–6. doi: 10.1128/jvi.51.1.1-6.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  60. Watanabe S., Yoshiike K. Inefficient expression in rat cells of transforming gene of BK virus with 68-bp tandem repeats in the viral promoter-enhancer. Virology. 1989 Mar;169(1):204–212. doi: 10.1016/0042-6822(89)90056-1. [DOI] [PubMed] [Google Scholar]
  61. White J. H., Metzger D., Chambon P. Expression and function of the human estrogen receptor in yeast. Cold Spring Harb Symp Quant Biol. 1988;53(Pt 2):819–828. doi: 10.1101/sqb.1988.053.01.093. [DOI] [PubMed] [Google Scholar]
  62. Yang R. C., Wu R. BK virus DNA: complete nucleotide sequence of a human tumor virus. Science. 1979 Oct 26;206(4417):456–462. doi: 10.1126/science.228391. [DOI] [PubMed] [Google Scholar]

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

RESOURCES