Abstract
JC virus (JCV) is the etiological agent of progressive multifocal leukoencephalopathy (PML), a fatal demyelinating disease of the central nervous system (CNS). During the acquired immunodeficiency syndrome (AIDS) epidemic, it was the cause of the death in up to 8% of AIDS patients. The genomic organization of JCV and, in particular, the hypervariability of the transcriptional control region (TCR), a regulatory noncoding region, are well known. Given that the TCR plays a central role in the viral replication of JCV, a crucial role in the determination of the neurotropism and in the pathogenic capabilities of the virus is also suspected. Here the authors describe a case of PML that did not respond to highly active antiretroviral therapy (HAART) therapy. There was a simultaneous presence of JCV strains with four different TCR structures in urine, peripheral blood cells, serum, and cerebrospinal fluid (CSF) samples. These data confirmed that the presence of the archetype TCR is restricted to urine, while also suggesting that the degree of the rearrangement varies and increases from the peripheral blood to CSF.
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Agostini HT, Ryschkewitsch CF, Singer EJ, Stoner GL (1997). JC virus regulatory region rearrangements and genotypes in progressive multifocal leukoencephalopathy. Two independent aspects of virus variation. J Gen Virol 78: 659–664.
Amemiya K, Treub R, Durham L, Major EO (1992). 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 267: 14204–14211.
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.
Ault GS, Stoner GL (1994). Brain and kidney of progressive multifocal leukoencephalopathy contain identical rearrangements of the JC virus promoter/enhancer. J Med Virol 44: 298–304.
Berger JR, Major EO (1999). Progressive multifocal leukoencephalopathy. Semin Neurol 19: 193–200.
Brooks BR, Walker DL (1984). Progressive multifocal leukoencephalopathy. Neurol Clin 2: 299–313.
Daniel AM, Swenson JJ, Mayreddy RPR, 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.
Elsner C, Dorries K (1998). Human polyomavirus JC control region variants in persistently infected CNS and kidney tissue. J Gen Virol 79: 789–799.
Ferrante P, Caldarelli-Stefano R, Omodeo Zorini E, Vago L, Boldorini R, Costanzi G (1995). PCR detection of JC virus DNA in brain tissue from patients with and without progressive multifocal leukoencephalopathy. J Med Virol 47: 219–225.
Ferrante P, Delbue S, Pagani E, Mancuso R, Marzocchetti A, Borghi E, Maserati R, Bestetti A, Cinque P (2003). Analysis of JC virus genotype distribution and transcriptional control region rearrangements in human immunodeficiency virus-positive progressive multifocal leukoencephalopathy patients with and without highly active antiretroviral treatment. J NeuroVirol 9 (Suppl 1): 42–46.
Ferrante P, Mediati M, Caldarelli-Stefano R, Losciale L, Mancuso R, Cagni AE, Maserati R (2001). Increased frequency of JC virus type 2 and of dual infection with JC virus type 1 and 2 in Italian progressive multifocal leukoencephalopathy patients. J NeuroVirol 7: 35–42.
Flaegstad T, Sundsfjord A, Arthur RR, Pedersen M, Traavik T, Subramani S (1991). Amplification and sequencing of the control regions of BK and JC virus from human urine by polymerase chain reaction. Virology 180: 553–560.
Frisque RJ, Bream G, Cannella MT (1984). Human polyomavirus JC virus genome. J Virol 51: 458–469.
Graff JR, Herman JG, Myohanen S, Baylin SB, Vertino PM (1997). Mapping patterns of CpG island methylation in normal and neoplastic cells implicates both upstream and downstream regions in de novo methylation. J Biol Chem 272: 22322–22329.
Iida T, Kitamura T, Guo J, Taguchi F, Aso Y, Nagashima K, Yogo Y (1993). Origin of JC polyomavirus variants associated with progressive multifocal leukoencephalopathy. Proc Natl Acad Sci U S A 90: 5062–5065.
Krachmarov CP, Chepenik LG, Barr-Vagell S, Khalili K, Johnson EM (1996). Activation of the JC virus Tat-responsive transcriptional control element by association of the Tat protein of human immunodeficiency virus 1 with cellular protein Puralpha. Proc Natl Acad Sci U S A 93: 14112–14117.
Macleod D, Charlton J, Mullins J, Bird AP (1994). Sp1 sites in the mouse aprt gene promoter are required to prevent methylation of the CpG island. Genes Dev 8: 2282–2292.
Newmann JT, Frisque RJ (1997). Detection of archetype and rearranged variants virus in multiple tissues from a pediatric PML patient. J Med Virol 52: 243–252.
Pagani E, Delbue S, Mancuso R, Borghi E, Tarantini L, Ferrante P (2003). Molecular analysis of JC virus genotypes circulating among the Italian healthy population. J NeuroVirol 9: 559–566.
Pfister LA, Letvin NL, Koralnik IJ (2001). JC virus regulatory region tandem repeats in plasma and central nervous system isolates correlate with poor clinical outcome in patients with progressive multifocal leukoencephalopathy. J Virol 75: 5672–5676.
Pietropaolo V, Videtta M, Fioriti D, Mischitelli M, Arancio A, Orsi N, Degener AM (2003). Rearrangement patterns of JC virus noncoding control region from different biological samples. J NeuroVirol 9: 603–611.
Rentier-Delrue F, Lubiniecki A, Howley PM (1981). Analysis of JC virus DNA purified directly from human progressive multifocal leukoencephalopathy brains. J Virol 38: 761–769.
Sadowska B, Barrucco R, Khalili K, Safak M (2003). Regulation of human polyomavirus JC virus gene transcription by AP-1 in Glial Cells. J Virol 1: 665–672.
Soldan SS, Berti R, Salem N, Secchiero P, Flamand L, Calabresi PA, Brennan MB, Maloni HW, McFarland HF, Lin H, Patnak M, Jacobson S (1997). Association of human herpes virus 6 (HHV-6) with multiple sclerosis: increased IgM response to HHV-6 early antigen and detection of serum HHV-6 DNA. Nat Med 3: 1394–1397.
Tada H, Lashgarlt M, Rappaport J, Khalili K (1989). Cell type-specific expression of JC virus early promoter is determined by positive and negative regulation. J Virol 63: 463–466.
Tamura T, Miura M, Ikenaka K, Mikoshiba K (1998). Analysis of transcription control elements of the mouse myelin basic protein gene in He-La cell extracts. Demonstration of a strong NF1 binding motif in the upstream region. Nucleic Acid Res 16: 11441–11459.
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.
Yogo Y, Sugimoto C (2001). The archetype concept and regulatory region rearrangement. In: Human polyomaviruses. Molecular and clinical perspectives. Khalili K, Stoner GL (eds). New York: Wiley-Liss, pp 491–526.
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This work was partially supported by NIH grant no. MH068360-01 and by a National Program of Research on AIDS 2001 grant from the Italian Institute of Health.
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Delbue, S., Sotgiu, G., Fumagalli, D. et al. A case of a progressive multifocal leukoencephalopathy patient with four different JC virus transcriptional control region rearrangements in cerebrospinal fluid, blood, serum, and urine. Journal of NeuroVirology 11, 51–57 (2005). https://doi.org/10.1080/13550280590900382
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DOI: https://doi.org/10.1080/13550280590900382