title: Epstein-Barr virus reactivation is induced, but abortive, in cutaneous lesions of systemic hydroa vacciniforme and hypersensitivity to mosquito bites.
abstract: BACKGROUND
  Epstein-Barr virus (EBV)-associated T/natural killer (NK)-lymphoproliferative disorders (LPDs) include hydroa vacciniforme (HV) and hypersensitivity to mosquito bites (HMB). The pathomechanisms of these diseases are still unclear.
  
  
  OBJECTIVE
  To understand the inflammatory process, we examined EBV reactivation markers, BZLF1 and BDRF1 mRNA in the tissue and blood from patients with EBV-associated T/NK-LPDs.
  
  
  METHODS
  Sixty-four patients with EBV-associated LPDs and epithelial neoplasms, and EBV+ cell line cells were studied. DNase-treated and resistant EBV DNA load in blood and cell culture supernatants were calculated. An EBV reactivation signal was analyzed in the tissue, blood and cell line cells.
  
  
  RESULTS
  In the tissue, BZLF1 mRNA was detected in 5 of 6 (83%) samples of EBV+ epithelial neoplasms, 16 of 21 (76%) of EBV+ lymphomas, and 5 of 15 (33%) of systemic HV and/or HMB, but negative in all 15 patients with classical HV. In the blood, BZLF1 mRNA was detected in only one of 19 (5.3%) samples of EBV-associated T/NK-LPDs. A down-stream reactivation signal, BDRF1 mRNA was expressed in all 6 samples of EBV+ epithelial neoplasms, but it was positive in only one of 15 (6.7%) samples from systemic HV and HMB in the tissue. EBV+ T/NK-cell line cells treated with phorbol 12-myristate 13-acetate produced BZLF1 and BDRF1 mRNA, and encapsidated EBV DNA was detected in the culture supernatants of cell line cells.
  
  
  CONCLUSIONS
  Stimulation-induced EBV reactivation occurred both in vivo and in vitro, but it was almost abortive in vivo. Reactivation-related EBV antigens might be responsible for induction of systemic HV and HMB.
authors.affiliation: Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama 700-8558, Japan; Department of Dermatology, Kawasaki Medical School, 577 Matsushima, Kurashiki 701-0192, Japan.
authors.forename: Takenobu
authors.initials: T
authors.lastname: Yamamoto
authors.affiliation: Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama 700-8558, Japan.
authors.forename: Yoji
authors.initials: Y
authors.lastname: Hirai
authors.affiliation: Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama 700-8558, Japan.
authors.forename: Tomoko
authors.initials: T
authors.lastname: Miyake
authors.affiliation: Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama 700-8558, Japan.
authors.forename: Toshihisa
authors.initials: T
authors.lastname: Hamada
authors.affiliation: Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama 700-8558, Japan.
authors.forename: Osamu
authors.initials: O
authors.lastname: Yamasaki
authors.affiliation: Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama 700-8558, Japan.
authors.forename: Shin
authors.initials: S
authors.lastname: Morizane
authors.affiliation: Department of Dermatology, Kawasaki Medical School, 577 Matsushima, Kurashiki 701-0192, Japan.
authors.forename: Wataru
authors.initials: W
authors.lastname: Fujimoto
authors.affiliation: Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama 700-8558, Japan. Electronic address: keijiiwa@cc.okayama-u.ac.jp.
authors.forename: Keiji
authors.initials: K
authors.lastname: Iwatsuki
mesh_terms: D000818:Animals; D000956:Antigens, Viral / Q000097:blood / Q000276:immunology; D036022:Capsid Proteins / Q000097:blood / Q000276:immunology; D009033:Culicidae; D004854:Herpesvirus 4, Human / Q000302:isolation & purification / Q000502:physiology*; D006801:Humans; D006837:Hydroa Vacciniforme / Q000276:immunology* / Q000821:virology; D006967:Hypersensitivity / Q000209:etiology*; D007299:Insect Bites and Stings / Q000150:complications / Q000276:immunology*; D007694:Killer Cells, Natural / Q000276:immunology; D008232:Lymphoproliferative Disorders / Q000276:immunology*; D012333:RNA, Messenger / Q000032:analysis; D012367:RNA, Viral / Q000032:analysis; D015534:Trans-Activators / Q000032:analysis
chemical_list: D000956:Antigens, Viral; C063676:BZLF1 protein, Herpesvirus 4, Human; D036022:Capsid Proteins; C041788:Epstein-Barr viral capsid antigen; D012333:RNA, Messenger; D012367:RNA, Viral; D015534:Trans-Activators
keywords: BDRF1; BZLF1; Epstein-Barr virus; Hydroa vacciniforme; Hypersensitivity to mosquito bites