Resveratrol inhibits Epstein Barr Virus lytic cycle in Burkitt's lymphoma cells by affecting multiple molecular targets.

Resveratrol (RV), a polyphenolic natural product present in many plants and fruits, exhibits anti-inflammatory, cardio-protective and anti-proliferative properties. Moreover, RV affects a wide variety of viruses including members of the Herpesviridae family, retroviruses, influenza A virus and polyomavirus by altering cellular pathways that affect viral replication itself. Epstein Barr Virus (EBV), the causative agent of infectious mononucleosis, is associated with different proliferative diseases in which it establishes a latent and/or a lytic infection. In this study, we examined the antiviral activity of RV against the EBV replicative cycle and investigated the molecular targets possibly involved. In a cellular context that allows in vitro EBV activation and lytic cycle progression through mechanisms closely resembling those that in vivo initiate and enable productive infection, we found that RV inhibited EBV lytic genes expression and the production of viral particles in a dose-dependent manner. We demonstrated that RV inhibited protein synthesis, decreased reactive oxygen species (ROS) levels, and suppressed the EBV-induced activation of the redox-sensitive transcription factors NF-kB and AP-1. Further insights into the signaling pathways and molecular targets modulated by RV may provide the basis for exploiting the antiviral activity of this natural product on EBV replication.