Virology Journal | |
Viral miRNAs in plasma and urine divulge JC polyomavirus infection | |
Lieven J Stuyver2  Luc Tritsmans1  Tom Van Loy2  Ole Lagatie2  | |
[1] Janssen Research and Development, Turnhoutseweg 30, Beerse 2340, Belgium;Janssen Diagnostics, Turnhoutseweg 30, Beerse 2340, Belgium | |
关键词: Viral activity; Biomarker; Progressive Multifocal Leukoencephalopathy; Circulating microRNA; Viral microRNA; JC Polyomavirus; | |
Others : 1148521 DOI : 10.1186/1743-422X-11-158 |
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received in 2014-06-18, accepted in 2014-08-25, 发布年份 2014 | |
【 摘 要 】
Background
JC polyomavirus (JCPyV) is a widespread human polyomavirus that usually resides latently in its host, but can be reactivated under immune-compromised conditions potentially causing Progressive Multifocal Leukoencephalopathy (PML). JCPyV encodes its own microRNA, jcv-miR-J1.
Methods
We have investigated in 50 healthy subjects whether jcv-miR-J1-5p (and its variant jcv-miR-J1a-5p) can be detected in plasma or urine.
Results
We found that the overall detection rate of JCPyV miRNA was 74% (37/50) in plasma and 62% (31/50) in urine. Subjects were further categorized based on JCPyV VP1 serology status and viral shedding. In seronegative subjects, JCPyV miRNA was found in 86% (12/14) and 57% (8/14) of plasma and urine samples, respectively. In seropositive subjects, the detection rate was 69% (25/36) and 64% (23/36) for plasma and urine, respectively. Furthermore, in seropositive subjects shedding virus in urine, higher levels of urinary viral miRNAs were observed, compared to non-shedding seropositive subjects (P < 0.001). No correlation was observed between urinary and plasma miRNAs.
Conclusion
These data indicate that analysis of circulating viral miRNAs divulge the presence of latent JCPyV infection allowing further stratification of seropositive individuals. Also, our data indicate higher infection rates than would be expected from serology alone.
【 授权许可】
2014 Lagatie et al.; licensee BioMed Central Ltd.
【 预 览 】
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【 参考文献 】
- [1]Ferenczy MW, Marshall LJ, Nelson CD, Atwood WJ, Nath A, Khalili K, Major EO: Molecular biology, epidemiology, and pathogenesis of progressive multifocal leukoencephalopathy, the JC virus-induced demyelinating disease of the human brain. Clin Microbiol Rev 2012, 25(3):471-506.
- [2]Bellizzi A, Nardis C, Anzivino E, Rodio D, Fioriti D, Mischitelli M, Chiarini F, Pietropaolo V: Human polyomavirus JC reactivation and pathogenetic mechanisms of progressive multifocal leukoencephalopathy and cancer in the era of monoclonal antibody therapies. J Neurovirol 2012, 18(1):1-11.
- [3]Frohman EM, Monaco MC, Remington G, Ryschkewitsch C, Jensen PN, Johnson K, Perkins M, Liebner J, Greenberg B, Monson N, Frohman TC, Douek D, Major EO: JC Virus in CD34+ and CD19+ Cells in Patients With Multiple Sclerosis Treated With Natalizumab. JAMA Neurol 2014, 71(5):596-602.
- [4]Markowitz RB, Thompson HC, Mueller JF, Cohen JA, Dynan WS: Incidence of BK virus and JC virus viruria in human immunodeficiency virus-infected and -uninfected subjects. J Infect Dis 1993, 167(1):13-20.
- [5]Tan CS, Dezube BJ, Bhargava P, Autissier P, Wuthrich C, Miller J, Koralnik IJ: Detection of JC virus DNA and proteins in the bone marrow of HIV-positive and HIV-negative patients: implications for viral latency and neurotropic transformation. J Infect Dis 2009, 199(6):881-888.
- [6]Chapagain ML, Nerurkar VR: Human polyomavirus JC (JCV) infection of human B lymphocytes: a possible mechanism for JCV transmigration across the blood-brain barrier. J Infect Dis 2010, 202(2):184-191.
- [7]Knowles WA, Pipkin P, Andrews N, Vyse A, Minor P, Brown DW, Miller E: Population-based study of antibody to the human polyomaviruses BKV and JCV and the simian polyomavirus SV40. J Med Virol 2003, 71(1):115-123.
- [8]Lee P, Plavina T, Castro A, Berman M, Jaiswal D, Rivas S, Schlain B, Subramanyam M: A second-generation ELISA (STRATIFY JCV DxSelect) for detection of JC virus antibodies in human serum and plasma to support progressive multifocal leukoencephalopathy risk stratification. J Clin Virol 2013, 57(2):141-146.
- [9]Major EO: Progressive multifocal leukoencephalopathy in patients on immunomodulatory therapies. Annu Rev Med 2010, 61:35-47.
- [10]Van Loy T, Thys K, Tritsmans L, Stuyver LJ: Quasispecies analysis of JC virus DNA present in urine of healthy subjects. PLoS One 2013, 8(8):e70950.
- [11]Padgett BL, Walker DL: Prevalence of antibodies in human sera against JC virus, an isolate from a case of progressive multifocal leukoencephalopathy. J Infect Dis 1973, 127(4):467-470.
- [12]Taguchi F, Kajioka J, Miyamura T: Prevalence rate and age of acquisition of antibodies against JC virus and BK virus in human sera. Microbiol Immunol 1982, 26(11):1057-1064.
- [13]Walker DL, Padgett BL: The epidemiology of human polyomaviruses. Prog Clin Biol Res 1983, 105:99-106.
- [14]Rudick RA, O’Connor PW, Polman CH, Goodman AD, Ray SS, Griffith NM, Jurgensen SA, Gorelik L, Forrestal F, Sandrock AW SEG: Assessment of JC virus DNA in blood and urine from natalizumab-treated patients. Ann Neurol 2010, 68(3):304-310.
- [15]Viscidi RP, Khanna N, Tan CS, Li X, Jacobson L, Clifford DB, Nath A, Margolick JB, Shah KV, Hirsch HH, Koralnik IJ: JC virus antibody and viremia as predictors of progressive multifocal leukoencephalopathy in human immunodeficiency virus-1-infected individuals. Clin Infect Dis: Offic Publ Infect Dis Soc Am 2011, 53(7):711-715.
- [16]Egli A, Infanti L, Dumoulin A, Buser A, Samaridis J, Stebler C, Gosert R, Hirsch HH: Prevalence of polyomavirus BK and JC infection and replication in 400 healthy blood donors. J Infect Dis 2009, 199(6):837-846.
- [17]Sormani MP, De Stefano N: Natalizumab discontinuation in the increasing complexity of multiple sclerosis therapy. Neurology 2014, 82(17):1484-1485.
- [18]Bloomgren G, Richman S, Hotermans C, Subramanyam M, Goelz S, Natarajan A, Lee S, Plavina T, Scanlon JV, Sandrock A, Bozic C: Risk of natalizumab-associated progressive multifocal leukoencephalopathy. N Engl J Med 2012, 366(20):1870-1880.
- [19]Cutter GR, Stuve O: Does risk stratification decrease the risk of natalizumab-associated PML? Where is the evidence? Mult Scler 2014, 20(10):1304-1305.
- [20]He L, Hannon GJ: MicroRNAs: small RNAs with a big role in gene regulation. Nat Rev Genet 2004, 5(7):522-531.
- [21]Boss IW, Renne R: Viral miRNAs: tools for immune evasion. Curr Opin Microbiol 2010, 13(4):540-545.
- [22]Kincaid RP, Sullivan CS: Virus-encoded microRNAs: an overview and a look to the future. PLoS Pathog 2012, 8(12):e1003018.
- [23]Leidinger P, Backes C, Deutscher S, Schmitt K, Mueller SC, Frese K, Haas J, Ruprecht K, Paul F, Stahler C, Lang CJ, Meder B, Bartfai T, Meese E, Keller A: A blood based 12-miRNA signature of Alzheimer disease patients. Genome Biol 2013, 14(7):R78. BioMed Central Full Text
- [24]Guay C, Regazzi R: Circulating microRNAs as novel biomarkers for diabetes mellitus. Nat Rev Endocrinol 2013, 9(9):513-521.
- [25]Madhavan D, Cuk K, Burwinkel B, Yang R: Cancer diagnosis and prognosis decoded by blood-based circulating microRNA signatures. Front Genet 2013, 4:116.
- [26]Lagatie O, Van Loy T, Tritsmans L, Stuyver LJ: Circulating human microRNAs are not linked to JC polyomavirus serology or urinary viral load in healthy subjects. Virol J 2014, 11(1):41. BioMed Central Full Text
- [27]Lagatie O, Tritsmans L, Stuyver LJ: The miRNA world of polyomaviruses. Virol J 2013, 10:268. BioMed Central Full Text
- [28]Seo GJ, Fink LH, O’Hara B, Atwood WJ, Sullivan CS: Evolutionarily conserved function of a viral microRNA. J Virol 2008, 82(20):9823-9828.
- [29]Bauman Y, Nachmani D, Vitenshtein A, Tsukerman P, Drayman N, Stern-Ginossar N, Lankry D, Gruda R, Mandelboim O: An identical miRNA of the human JC and BK polyoma viruses targets the stress-induced ligand ULBP3 to escape immune elimination. Cell Host Microbe 2011, 9(2):93-102.
- [30]Kawano Y, Iwata S, Kawada J, Gotoh K, Suzuki M, Torii Y, Kojima S, Kimura H, Ito Y: Plasma viral microRNA profiles reveal potential biomarkers for chronic active Epstein-Barr virus infection. J Infect Dis 2013, 208(5):771-779.
- [31]Chugh PE, Sin SH, Ozgur S, Henry DH, Menezes P, Griffith J, Eron JJ, Damania B, Dittmer DP: Systemically circulating viral and tumor-derived microRNAs in KSHV-associated malignancies. PLoS Pathog 2013, 9(7):e1003484.
- [32]Link A, Balaguer F, Nagasaka T, Boland CR, Goel A: MicroRNA miR-J1-5p as a potential biomarker for JC virus infection in the gastrointestinal tract. PLoS One 2014, 9(6):e100036.
- [33]Chen C, Ridzon DA, Broomer AJ, Zhou Z, Lee DH, Nguyen JT, Barbisin M, Xu NL, Mahuvakar VR, Andersen MR, Lao KQ, Livak KJ, Guegler KJ: Real-time quantification of microRNAs by stem-loop RT-PCR. Nucleic Acids Res 2005, 33(20):e179.
- [34]Major EO, Frohman E, Douek D: JC viremia in natalizumab-treated patients with multiple sclerosis. N Engl J Med 2013, 368(23):2240-2241.
- [35]Major EO, Frohman E, Douek D: More on JC viremia in natalizumab-treated patients with multiple sclerosis. N Engl J Med 2013, 369(13):1280.
- [36]Berger JR, Houff SA, Gurwell J, Vega N, Miller CS, Danaher RJ: JC virus antibody status underestimates infection rates. Ann Neurol 2013, 74(1):84-90.
- [37]Gorelik L, Reid C, Testa M, Brickelmaier M, Bossolasco S, Pazzi A, Bestetti A, Carmillo P, Wilson E, McAuliffe M, Tonkin C, Carulli JP, Lugovskoy A, Lazzarin A, Sunyaev S, Simon K, Cinque P: Progressive multifocal leukoencephalopathy (PML) development is associated with mutations in JC virus capsid protein VP1 that change its receptor specificity. J Infect Dis 2011, 204(1):103-114.
- [38]Reid CE, Li H, Sur G, Carmillo P, Bushnell S, Tizard R, McAuliffe M, Tonkin C, Simon K, Goelz S, Cinque P, Gorelik L, Carulli JP: Sequencing and analysis of JC virus DNA from natalizumab-treated PML patients. J Infect Dis 2011, 204(2):237-244.
- [39]Fedele CG, Ciardi MR, Delia S, Contreras G, Perez JL, De Ona M, Vidal E, Tenorio A: Identical rearranged forms of JC polyomavirus transcriptional control region in plasma and cerebrospinal fluid of acquired immunodeficiency syndrome patients with progressive multifocal leukoencephalopathy. J Neurovirol 2003, 9(5):551-558.
- [40]Sullivan CS, Grundhoff AT, Tevethia S, Pipas JM, Ganem D: SV40-encoded microRNAs regulate viral gene expression and reduce susceptibility to cytotoxic T cells. Nature 2005, 435(7042):682-686.
- [41]Broekema NM, Imperiale MJ: miRNA regulation of BK polyomavirus replication during early infection. Proc Natl Acad Sci U S A 2013, 110(20):8200-8205.
- [42]Tian YC, Li YJ, Chen HC, Wu HH, Weng CH, Chen YC, Lee CC, Chang MY, Hsu HH, Yen TH, Hung CC, Yang CW: Polyomavirus BK-encoded microRNA suppresses autoregulation of viral replication. Biochem Biophys Res Commun 2014, 447(3):543-549.
- [43]Sullivan CS, Sung CK, Pack CD, Grundhoff A, Lukacher AE, Benjamin TL, Ganem D: Murine polyomavirus encodes a microRNA that cleaves early RNA transcripts but is not essential for experimental infection. Virology 2009, 387(1):157-167.
- [44]Lagana A, Russo F, Veneziano D, Bella SD, Giugno R, Pulvirenti A, Croce CM, Ferro A: Extracellular circulating viral microRNAs: current knowledge and perspectives. Front Genet 2013, 4:120.
- [45]Umbach JL, Kramer MF, Jurak I, Karnowski HW, Coen DM, Cullen BR: MicroRNAs expressed by herpes simplex virus 1 during latent infection regulate viral mRNAs. Nature 2008, 454(7205):780-783.
- [46]Yang HJ, Huang TJ, Yang CF, Peng LX, Liu RY, Yang GD, Chu QQ, Huang JL, Liu N, Huang HB, Zhu ZY, Qian CN, Huang BJ: Comprehensive profiling of Epstein-Barr virus-encoded miRNA species associated with specific latency types in tumor cells. Virol J 2013, 10:314. BioMed Central Full Text
- [47]Li JY, McNicholas K, Yong TY, Rao N, Coates PT, Higgins GD, Carroll RP, Woodman RJ, Michael MZ, Gleadle JM: BK virus encoded microRNAs are present in blood of renal transplant recipients with BK viral nephropathy. Am J Transplant: Offic J Am Soc Transplant Am Soc Transplant Surgeons 2014, 14(5):1183-1190.
- [48]Griffiths-Jones S: The microRNA registry. Nucleic Acids Res 2004, 32(Database issue):D109-D111.
- [49]Stuyver LJ, Verbeke T, Van Loy T, Van Gulck E, Tritsmans L: An antibody response to human polyomavirus 15-mer peptides is highly abundant in healthy human subjects. Virol J 2013, 10:192. BioMed Central Full Text