TY - JOUR
T1 - Epstein-Barr virus reactivation is induced, but abortive, in cutaneous lesions of systemic hydroa vacciniforme and hypersensitivity to mosquito bites
AU - Yamamoto, Takenobu
AU - Hirai, Yoji
AU - Miyake, Tomoko
AU - Hamada, Toshihisa
AU - Yamasaki, Osamu
AU - Morizane, Shin
AU - Fujimoto, Wataru
AU - Iwatsuki, Keiji
N1 - Funding Information:
This work was supported by Grant-in-Aid for Research Activity Start-up from Japan Society for the Promotion of Science ( 23890238 ), Grant-in-Aid for Scientific Research (C) from the Ministry of Education, Culture, Sports, Science and Technology (MEXT) ( 15K09744 ), Grant for research on Practical Research Project for Rare/Intractable Diseases ( 15ek0109098 ) ( 15ek010912401 ) from Japan Agency for Medical Research and Development (AMED) and Grant for Research on Measures for Intractable Diseases from the Ministry of Health, Labours and Welfare (MHLW) ( H26-071 ).
Publisher Copyright:
© 2016 Japanese Society for Investigative Dermatology.
PY - 2016/6/1
Y1 - 2016/6/1
N2 - 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. Conclusion: 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.
AB - 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. Conclusion: 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.
KW - BDRF1
KW - BZLF1
KW - Epstein-Barr virus
KW - Hydroa vacciniforme
KW - Hypersensitivity to mosquito bites
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U2 - 10.1016/j.jdermsci.2016.03.001
DO - 10.1016/j.jdermsci.2016.03.001
M3 - Article
C2 - 27039668
AN - SCOPUS:84962068704
SN - 0923-1811
VL - 82
SP - 153
EP - 159
JO - Journal of dermatological science
JF - Journal of dermatological science
IS - 3
ER -
