Abstract
Polyomavirus JC (JCPyV) reactivation and development of progressive multifocal leukoencephalopathy is a health concern in multiple sclerosis patients under natalizumab therapy. Here, the JCPyV microRNA-J1-3p and microRNA-J1-5p expressions and genomic variability were investigated in blood and urine samples of multiple sclerosis patients before and under natalizumab therapy and in healthy controls. The two JCPyV microRNAs were detected in the JCPyV-DNA-positive peripheral blood mononuclear cell samples and in the exosomes derived from plasma and urine obtained from JCPyV-DNA-positive and JCPyV-DNA-negative patients. In particular, the increased JCPyV microRNA expression in samples of multiple sclerosis patients under natalizumab therapy was consistent with the high JCPyV-DNA positivity observed in these samples. Moreover, JCPyV microRNA genomic region showed few nucleotide differences in samples obtained from blood and urine of multiple sclerosis patients and healthy controls. Overall, these data suggest a potential role of the JCPyV microRNA expression in counteracting the viral reactivation to maintain JCPyV asymptomatic persistence in the host.
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References
Bauman Y, Mandelboim O (2011) MicroRNA based immunoevasion mechanism of human polyomaviruses. RNA Biol 8:591–594
Bauman Y, Nachmani D, Vitenshtein A, Tsukerman P, Drayman N, Stern-Ginossar N, Lankry D, Gruda R, Mandelboim O (2011) An identical miRNA of the human JC and BK polyoma viruses targets the stress-induced ligand ULBP3 to escape immune elimination. Cell Host Microbe 9:93–102
Bloomgren G, Richman S, Hotermans C, Subramanyam M, Goelz S, Natarajan A, Lee S, Plavina T, Scanlon JV, Sandrock A, Bozic C (2012) Risk of natalizumab-associated progressive multifocal leukoencephalopathy. N Engl J Med 366:1870–1880
Boss IW, Renne R (2011) Viral miRNAs and immune evasion. Biochim Biophys Acta 1809:708–714
Broekema NM, Imperiale MJ (2013) miRNA regulation of BK polyomavirus replication during early infection. Proc Natl Acad Sci U S A 110:8200–8205
Chen Y, Bord E, Tompkins T, Miller J, Tan CS, Kinkel RP, Stein MC, Viscidi RP, Ngo LH, Koralnik IJ (2009) Asymptomatic reactivation of JC virus in patients treated with natalizumab. N Engl J Med 361:1067–1074
Chen CJ, Cox JE, Kincaid RP, Martinez A, Sullivan CS (2013) Divergent MicroRNA targetomes of closely related circulating strains of a polyomavirus. J Virol 87:11135–11147
Ferenczy MW, Marshall LJ, Nelson CD, Atwood WJ, Nath A, Khalili K, Major EO (2012) Molecular biology, epidemiology, and pathogenesis of progressive multifocal leukoencephalopathy, the JC virus-induced demyelinating disease of the human brain. Clin Microbiol Rev 25:471–506
Imperiale MJ (2014) Polyomavirus miRNAs: the beginning. Curr Opin Virol 7C:29–32
Lagatie O, Tritsmans L, Stuyver LJ (2013) The miRNA world of polyomaviruses. Virol J 10:268–288
Lagatie O, Van Loy T, Tritsmans L, Stuyver LJ (2014) Viral miRNAs in plasma and urine divulge JC polyomavirus infection. Virol J 11:158–166
Lindberg RL, Achtnichts L, Hoffmann F, Kuhle J, Kappos L (2008) Natalizumab alters transcriptional expression profiles of blood cell subpopulations of multiple sclerosis patients. J Neuroimmunol 194:153–164
Link A, Balaguer F, Nagasaka T, Boland CR, Goel A (2014) MicroRNA miR-J1-5p as a potential biomarker for JC virus infection in the gastrointestinal tract. PLoS ONE 9:e100036
Pegtel DM, Cosmopoulos K, Thorley-Lawson DA, van Eijndhoven MA, Hopmans ES, Lindenberg JL, de Gruijl TD, Würdinger T, Middeldorp JM (2010) Functional delivery of viral miRNAs via exosomes. Proc Natl Acad Sci U S A 107:6328–6333
Ryschkewitsch CF, Jensen PN, Major EO (2013) Multiplex qPCR assay for ultra sensitive detection of JCV DNA with simultaneous identification of genotypes that discriminates non-virulent from virulent variants. J Clin Virol 57:243–248
Sadiq SA, Puccio LM, Brydon EW (2010) JCV detection in multiple sclerosis patients treated with natalizumab. J Neurol 257:954–958
Seo GJ, Fink LH, O’Hara B, Atwood WJ, Sullivan CS (2008) Evolutionarily conserved function of a viral microRNA. J Virol 82:9823–9828
Skarica M, Eckstein C, Whartenby KA, Calabresi PA (2011) Novel mechanisms of immune modulation of natalizumab in multiple sclerosis patients. J Neuroimmunol 235:70–76
Valadi H, Ekström K, Bossios A, Sjöstrand M, Lee JJ, Lötvall JO (2007) Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells. Nat Cell Biol 9:654–659
Zhang S, Sroller V, Zanwar P, Chen CJ, Halvorson SJ, Ajami NJ, Hecksel CW, Swain JL, Wong C, Sullivan CS, Butel JS (2014) Viral microRNA effects on pathogenesis of polyomavirus SV40 infections in Syrian golden hamsters. PLoS Pathog 10:e1003912
Acknowledgments
The work was supported by grants from the Fondazione “Istituto di Ricerca Virologica Oretta Bartolomei Corsi” Florence, Italy.
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All authors declare that that they have no conflict of interest.
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Giovannelli, I., Martelli, F., Repice, A. et al. Detection of JCPyV microRNA in blood and urine samples of multiple sclerosis patients under natalizumab therapy. J. Neurovirol. 21, 666–670 (2015). https://doi.org/10.1007/s13365-015-0325-3
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DOI: https://doi.org/10.1007/s13365-015-0325-3