Epstein-Barr virus reactivation is induced, but abortive, in cutaneous lesions of systemic hydroa vacciniforme and hypersensitivity to mosquito bites

• EBV reactivation occurs in the cutaneous lesions of hydroa vacciniforme (HV) and hypersensitivity to mosquito bites (HMB), but seldom in blood.
• The down-stream signals of EBV reactivation occurred frequently in EBV+ epithelial neoplasm.
• Unlike the in vitro study, the reactivation cascade of HV and HMB is usually abortive in the cutaneous lesions probably because of host immune responses.

BackgroundEpstein-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.ObjectiveTo 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.MethodsSixty-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.ResultsIn 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.ConclusionStimulation-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.