title: Plasma viral microRNA profiles reveal potential biomarkers for chronic active Epstein-Barr virus infection.
abstract: BACKGROUND
  Chronic active Epstein-Barr virus (CAEBV) infection has high mortality and morbidity, and biomarkers for disease severity and prognosis are required. MicroRNAs (miRNAs) are small noncoding RNAs, and EBV encodes multiple miRNAs. Because plasma contains sufficiently stable miRNAs, circulating EBV-associated miRNA profiles were investigated as novel biomarkers in CAEBV infection.
  
  
  METHODS
  Plasma miRNA expression was assessed for 12 miRNAs encoded within 2 EBV open reading frames (BART and BHRF). Expression levels were investigated in 19 patients with CAEBV infection, 14 patients with infectious mononucleosis, and 11 healthy controls. Relative expression levels of plasma miRNAs were determined by TaqMan probe-based quantitative assay.
  
  
  RESULTS
  Plasma miR-BART1-5p, 2-5p, 5, and 22 levels in patients with CAEBV infection were significantly greater than those in patients with infectious mononucleosis and in controls. Plasma miR-BART2-5p, 4, 7, 13, 15, and 22 levels were significantly elevated in patients with CAEBV infection with systemic symptoms, compared with levels in patients with no systemic symptoms. The levels of miR-BART2-5p, 13, and 15 showed clinical cutoff values associated with specific clinical conditions, in contrast to plasma EBV loads.
  
  
  CONCLUSIONS
  Levels of specific plasma EBV miRNAs were elevated differentially in patients with CAEBV infection. Several EBV miRNAs, particularly miR-BART2-5p, 13, and 15, are potentially biomarkers of disease severity or prognosis.
authors.affiliation: Department of Pediatrics, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Kawano
authors.forename: Seiko
authors.initials: S
authors.lastname: Iwata
authors.forename: Jun-ichi
authors.initials: J
authors.lastname: Kawada
authors.forename: Kensei
authors.initials: K
authors.lastname: Gotoh
authors.forename: Michio
authors.initials: M
authors.lastname: Suzuki
authors.forename: Yuka
authors.initials: Y
authors.lastname: Torii
authors.forename: Seiji
authors.initials: S
authors.lastname: Kojima
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kimura
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Ito
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood*; D002648:Child; D002675:Child, Preschool; D020031:Epstein-Barr Virus Infections / Q000175:diagnosis*; D005260:Female; D004854:Herpesvirus 4, Human / Q000235:genetics*; D006801:Humans; D007223:Infant; D008297:Male; D035683:MicroRNAs / Q000097:blood*; D008875:Middle Aged; D010949:Plasma / Q000821:virology*; D012367:RNA, Viral / Q000097:blood*; D055815:Young Adult
chemical_list: D015415:Biomarkers; D035683:MicroRNAs; D012367:RNA, Viral
keywords: Epstein–Barr virus; biomarker; chronic active Epstein–Barr virus infection; microRNA