Skip to main content
Log in

A classification scheme for human polyomavirus JCV variants based on the nucleotide sequence of the noncoding regulatory region

  • Basic Science and Immunobiology Report
  • Published:
Journal of NeuroVirology Aims and scope Submit manuscript

Abstract

The human polyomavirus JCV is responsible for the central nervous system (CNS) demyelination observed in cases of progressive multifocal leukoencephalopathy (PML). Lytic infection of oligodendrocytes, the cells that constitute the basis of myelin in the CNS, is established by JCV in conjunction with immunosuppressive conditions. Beyond this, however, many questions related to JCV pathogenesis remain unanswered. The JCV regulatory region is a hypervariable noncoding sequence positioned between the early and late protein-coding regions. The particular nucleotide sequence of a JCV regulatory region affects levels of viral transcription and replication. Modifications to this promoter/enhancer structure can alter the cellular host range and may be responsible for switching JCV between states of lytic and latent infection. The regulatory region structure has, therefore, been used to distinguish JCV variants. Nucleotide sequencing studies have uncovered numerous variations of regulatory region structure. Until now, however, no inclusive nomenclature existed that linked variants by regulatory region structure and/or activity. We have arranged all known variant JCV regulatory regions into quadrants according to the integration of particular sequence sections and repetition of sequence section groups. This arrangement of regulatory regions results in an updated nomenclature that is well-suited for describing the relationships between JCV variants. Four distinct structural forms (I-S, I-R, II-S, and II-R) are defined along with tissue tropisms. This design provides logical connections between the variant regulatory regions and may be useful for elucidating crucial steps in JCV pathogenesis.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Ault GS (1997). Activity of JC virus archetype and PML-type regulatory regions in glial cells. J Gen Virol 78: 163–169.

    CAS  PubMed  Google Scholar 

  • Ault GS, Stoner GL (1993). Human polyomavirus JC promoter/enhancer rearrangement patterns from progressive multifocal leukoencephalopathy brain are unique derivatives of a single archetypal structure. J Gen Virol 74: 1499–1507.

    Article  CAS  PubMed  Google Scholar 

  • Bofill-Mas S, Pina S, Girones R (2000). Documenting the epidemiologic patterns of polyomaviruses in human populations by studying their presence in urban sewage. Appl Environ Microbiol 66: 238–245.

    Article  CAS  PubMed  Google Scholar 

  • Chang C-F, Gallia GL, Muralidharan V, Chen NN, Zoltick P, Johnson E, Khalili K (1996). Evidence that replication of human neurotropic JC virus DNA in glial cells is regulated by the sequence-specific single-stranded DNA-binding protein Pur α. J Virol 70: 4150–4156.

    CAS  PubMed  Google Scholar 

  • Chang D, Sugimoto, Wang M, Tsai R-T, Yogo Y (1999). JC virus genotypes in a Taiwan aboriginal tribe (Bunun): implications for its population history. Arch Virol 144: 1081–1090.

    Article  CAS  PubMed  Google Scholar 

  • Ciappi S, Azzi A, De Santis R, Leoncini F, Sterrantino G, Mazzotta F, Mecocci L (1999). Archetypal and rearranged sequences of human polyomavirus JC transcription control region in peripheral blood leukocytes and in cerebrospinal fluid. J Gen Virol 80: 1017–1023.

    CAS  PubMed  Google Scholar 

  • Daniel AM, Swenson JJ, Mayreddy RP, Khalili K, Frisque RJ (1996). Sequences within the early and late promoters of archetype JC virus restrict viral DNA replication and infectivity. Virology 216: 90–101.

    Article  CAS  PubMed  Google Scholar 

  • Eisner C, Dörries K (1998). Human polyomavirus JC control region variants in persistently infected CNS and kidney tissue. J Gen Virol 79: 789–799.

    Google Scholar 

  • Feigenbaum L, Khalili K, Major E, Khoury G (1987). Regulation of the host range of human papovavirus JCV. Proc Natl Acad Sci USA 84: 3695–3698.

    Article  CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  • Gilbert JM, Benjamin TL (2000). Early steps of polyomavirus entry into cells. J Virol 74: 8582–8588.

    Article  CAS  PubMed  Google Scholar 

  • Gronostajski RM (2000). Roles of the NFI/CTF gene family in transcription and development. Gene 249: 31–45.

    Article  CAS  PubMed  Google Scholar 

  • Hara K, Sugimoto C, Kitamura T, Aoki N, Taguchi F, Yogo Y (1998). Archetype JC virus efficiently replicates in COS-7 cells, simian cells constitutively expressing simian virus 40 T antigen. J Virol 72: 5335–5342.

    CAS  PubMed  Google Scholar 

  • Houff SA, Major EO, Katz DA, Kufta CV, Sever JL, Pittaluga S, Roberts JR, Gitt J, Saini N, Lux W (1998). Involvement of JC virus-infected mononuclear cells from the bone marrow and spleen in the pathogenesis of progressive multifocal leukoencephalopathy. N Engl J Med 318: 301–305.

    Article  Google Scholar 

  • Jensen PN, Major EO (1999). Viral variant nucleotide sequences help expose leukocytic positioning in the JC virus pathway to the CNS. J Leuk Bio 65: 428–438.

    CAS  Google Scholar 

  • Kato A, Sugimoto C, Zheng H-Y, Kitamura T, Yogo Y (2000). Lack of disease-specific amino acid changes in the viral proteins of JC virus isolates from the brain with progressive multifocal leukoencephalopathy. Arch Virol 145: 2173–2182.

    Article  CAS  PubMed  Google Scholar 

  • Krynska B, del Valle L, Gordon J, Otte J, Croul S, Khalili K (2000). Identification of a novel p53 mutation in JCV-induced mouse medulloblastoma. Virology 274: 65–74.

    Article  CAS  PubMed  Google Scholar 

  • Laghi L, Randolph AE, Chauhan DP, Marra G, Major EO, Neel JV, Boland CR (1999). JC virus DNA is present in the mucosa of the human colon and in colorectal cancers. Proc Natl Acad Sci USA 96: 7484–7489.

    Article  CAS  PubMed  Google Scholar 

  • Liu CK, Wei G, Atwood WJ (1998). Infection of glial cells by the human polyomavirus JC is mediated by an N-linked glycoprotein containing terminal α(2–6)-linked sialic acids. J Virol 72: 4643–4649.

    CAS  PubMed  Google Scholar 

  • Major EO, Amemiya K, Tornatore CS, Houff SA, Berger JR (1992). Pathogenesis and molecular biology of progressive multifocal leukoencephalophathy, the JC virus-induced demyelinating disease of the human brain. Clin Microbiol Rev 5: 49–73.

    CAS  PubMed  Google Scholar 

  • Mandl C, Walker DL, Frisque RJ (1987). Derivation and characterization of POJ cells, transformed human fetal glial cells that retain their permissivity for JC virus. J Virol 61: 755–763.

    CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  • Mayreddy RP, Safak M, Razmara M, Zoltick P, Khalili K (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. J Virol 70: 2387–2393.

    CAS  PubMed  Google Scholar 

  • Monaco MCG, Jensen PN, Hou J, Durham LC, Major EO (1998). Detection of JC virus DNA in human tonsil tissue: evidence for site of initial viral infection. J Virol 72: 9918–9923.

    CAS  PubMed  Google Scholar 

  • Newman JT, Frisque RJ (1999). Identification of JC virus variants in multiple tissues of pediatric and adult PML patients. J Med Virol 58: 79–86.

    Article  CAS  PubMed  Google Scholar 

  • Okada Y, Sawa H, Tanaka S, Takada A, Suzuki S, Hasegawa H, Takashi U, Fujisawa J-I, Tanaka Y, Hall WW, Nagashima K (2000). Transcriptional activation of JC virus by human T-lymphotropic virus type I Tax protein in human neuronal cell lines. J Bio Chem 275: 17016–17023.

    Article  CAS  Google Scholar 

  • Osborn JE, Robertson SM, Padgett BL, ZuRhein GM, Walker DL, Weisblum B (1974). Comparison of JC and BK human papovaviruses with simian virus 40: restriction endonuclease digestion and gel electrophoresis of resultant fragments. J Virol 13: 614–622.

    CAS  PubMed  Google Scholar 

  • Pho MT, Ashok A, Atwood WJ (2000). JC virus enters human glial cells by clathrin-dependent receptor-mediated endocytosis. J Virol 74: 2288–2292.

    Article  CAS  PubMed  Google Scholar 

  • Rencic A, Gordon J, Otte J, Curtis M, Kovatich A, Zoltick P, Khalili K, Andrews D (1996). Detection of JC virus DNA sequence and expression of the viral oncoprotein, tumor antigen, in brain of immunocompetent patient with oligoastrocytoma. Proc Natl Acad Sci USA 93: 7352–7357.

    Article  CAS  PubMed  Google Scholar 

  • Ricciardiello L, Chang DK, Laghi L, Goel A, Chang CL, Boland CR (2001). Mad-1 is the exclusive JC virus strain present in the human colon, and its transcriptional control region has a deleted 98-base-pair sequence in colon cancer tissues. J Virol 75: 1996–2001.

    Article  CAS  PubMed  Google Scholar 

  • Safak M, Gallia GL, Ansari SA, Khalili K (1999a). Physical and functional interaction between the Y-box binding protein YB-1 and human polyomavirus JC virus large T antigen. J Virol 73: 10146–10157.

    CAS  PubMed  Google Scholar 

  • Safak M, Gallia GL, Khalili K (1999b). A 23-bp sequence element from human neurotropic JC virus is responsive to NF-κB subunits. Virology 262: 178–189.

    Article  CAS  PubMed  Google Scholar 

  • Shinohara T, Nagashima K, Major EO (1997). Propagation of the human polyomavirus, JCV, in human neuroblastoma cell lines. Virology 228: 269–277.

    Article  CAS  PubMed  Google Scholar 

  • Shishido-Hara Y, Hara Y, Larson T, Yasui K, Nagashima K, Stoner GL (2000). Analysis of capsid formation of human polyomavirus JC (Tokyo-1 strain) by a eukaryotic expression system: splicing of late RNAs, translation and nuclear transport of major capsid protein VP1, and capsid assembly. J Virol 74: 1840–1853.

    Article  CAS  PubMed  Google Scholar 

  • Sugimoto C, Ito D, Tanaka K, Matsuda H, Saito H, Sakai H, Fujihara K, Itoyama Y, Yamada T, Kira J, Matsumoto R, Mori M, Nagashima K, Yogo Y (1998). Amplification of JC virus regulatory DNA sequences from cerebrospinal fluid: diagnostic value for progressive multifocal leukoencephalopathy. Arch Virol 143: 249–262.

    Article  CAS  PubMed  Google Scholar 

  • Sumner C, Shinohara T, Durham L, Traub R, Major EO, Amemiya K (1996). Expression of multiple classes of the nuclear factor-1 family in the developing human brain: differential expression of two classes of NF-1 genes. J NeuroVirol 2: 87–100.

    Article  CAS  PubMed  Google Scholar 

  • Vacante DA, Traub R, Major EO (1989). Extension of JC virus host range to monkey cells by insertion of a simian virus 40 enhancer into the JC virus regulatory region. Virology 170: 353–361.

    Article  CAS  PubMed  Google Scholar 

  • Vaz B, Cinque P, Pickhardt M, Weber T (2000). Analysis of the transcriptional control region in progressive multi-focal leukoencephalopathy. J NeuroVirol 6: 398–409.

    Article  CAS  PubMed  Google Scholar 

  • Winklhofer KF, Albrecht I, Wegner M, Heilbronn R (2000). Human cytomegalovirus immediate-earlygene 2 expression leads to JCV replication in nonpermissive cells via transcriptional activation of JCV T antigen. Virology 275: 323–334.

    Article  CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Eugene O. Major.

Additional information

This article is not subject to U.S. copyright laws.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Jensen, P.N., Major, E.O. A classification scheme for human polyomavirus JCV variants based on the nucleotide sequence of the noncoding regulatory region. Journal of NeuroVirology 7, 280–287 (2001). https://doi.org/10.1080/13550280152537102

Download citation

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1080/13550280152537102

Keywords

Navigation