Transcription of the Epstein–Barr Virus Lytic Cycle Activator BZLF-1 During Oxidative Stress Induction

Abstract

While latent Epstein-Barr virus infection can be in vitro reactivated by various reagents such as 12-0-tetradecanoylphorbol-13-acetate and calcium ionophore, relatively little is known about in vivo physiological and biochemical factors implicated in this reactivation. Previous studies have described an association between oxidative stress and Epstein-Barr virus infection. In this present study, we investigated the effect of oxidative stress inductors: H2O2 and FeSO4 on reactivation of EBV through BZLF-1 gene expression. Oxidative stress was induced in Raji cell line with 0.2 mM H2O2 or with 0.1 mM FeSO4, and assessed by malondialdehyde level determination, as well as superoxide dismutase and catalase genes expression. Simultaneously, the expression of Epstein-Barr virus immediate-early gene BZLF-1 was analyzed by RT-PCR after 6, 12, 24, 36, and 48 h after H2O2 or FeSO4 treatment. Oxidative stress was evidenced in the Raji cell line by high MDA level as well as superoxide dismutase and catalase genes up-regulation. The transcripts of BZLF-1 were detected from 6 h after 30 min of H2O2 or FeSO4 treatment and maintained until 48 h. These results strongly suggest that oxidative stress contributes to the reactivation of EBV lytic cycle, through induction of BZLF-1 gene expression, a process that may play an important role in the pathogenesis of EBV-associated diseases.