Ble-stranded DNA linear molecule that encodes more than 100 viral proteins, although in latent infected cells only a limited number of gene products are expressed and these include six EBV nuclear antigens (EBNA1, -2, -3A, -3B, -3C, and -LP), three latent membrane proteins (LMP1, -2A, -and 2B), and two small nonpolyadenylated RNAs EBER 1 and 2 [3]. Two viral products, EBNA2 and LMP1, are absolutely required for the in vitro transformation of B cells whereas EBNA1, EBNA3A and EBNAC are not indispensable, but nevertheless play a crucial role in the B cells transformation process [3]. Other EBV factors,including the viral Bcl-2 analogous BALF1 and BHRF1, also play critical roles in B-cell transformation since their very early expression after infection, prevents EBV-infected B cells from undergoing apoptosis [4]. Primary EBV infection, which usually occurs in childhood, is generally asymptomatic; however EBV infection may cause infectious mononucleosis when acquired in adolescence or adulthood. EBV persists for life in the memory B cells compartment and reactivation of EBV is prevented by an Dimethylenastron effective immunosurveillance mediated through virus-specific T-cell immunity [5]. However, infected B cells can proliferate without control in the absence of an effective immune response, resulting in malignant transformation. This process is exemplified by the development PTLD or lymphoproliferative disorders in patients undergoing immunosuppressive therapy for other medical conditions [6,7]. Currently, reactivation of EBV is an increasing complication in immune deficient patients, particularly after HSCT or SOT [7]. Whereas the tapering of immunosuppression, donor lymphocyte infusion, and rituximab may be effective for this complication after HSCT, severe adverse events such as fatal graft-versus-host disease and infections could develop thereafter [8,9], therefore effective but less toxic anti-EBV therapies are needed.Resveratrol Prevents EBV-Transformation of B CellsResveratrol (3, 49, 5 tri-hydroxystilbene) is a naturally occurring polyphenol found in red wine, grapes and other sources [10]. Numerous health benefits have been associated with resveratrol including anti-inflammatory, anti-aging and antitumor activities [10,11]. The broad anti-cancer activities of resveratrol are exerted by a particular property of this 4EGI-1 compound to target multiple proteins including the NFkB, STAT-3, and AKT pathways which are all involved in the regulation of cell proliferation, survival and apoptosis [11?3]. Several studies have reported inhibitory activities of resveratrol against various virus including herpes simplex virus 1 and 2, Varicella zoster virus, human cytomegalovirus, and influenza virus, however, the mechanisms for such antiviral properties have not been clearly defined [14,15]. The current study investigated the potential antiviral effects of resveratrol against EBV, and focused on the modulation of the oncogenic properties of this virus. This study took advantage of the ability of EBV to transform B cells into lymphoblastoid cell lines (LCL) in vitro, which recapitulates many aspect of the EBV-related malignant transformation. The data revealed that resveratrol effectively prevented the EBV-induced transformation of B cells, which was mediated by the inhibitory effects of resveratrol on multiple genes involved in transformation and survival of human B cells. This is the first report to show mechanistic insights into the efficacy of resveratrol to pr.Ble-stranded DNA linear molecule that encodes more than 100 viral proteins, although in latent infected cells only a limited number of gene products are expressed and these include six EBV nuclear antigens (EBNA1, -2, -3A, -3B, -3C, and -LP), three latent membrane proteins (LMP1, -2A, -and 2B), and two small nonpolyadenylated RNAs EBER 1 and 2 [3]. Two viral products, EBNA2 and LMP1, are absolutely required for the in vitro transformation of B cells whereas EBNA1, EBNA3A and EBNAC are not indispensable, but nevertheless play a crucial role in the B cells transformation process [3]. Other EBV factors,including the viral Bcl-2 analogous BALF1 and BHRF1, also play critical roles in B-cell transformation since their very early expression after infection, prevents EBV-infected B cells from undergoing apoptosis [4]. Primary EBV infection, which usually occurs in childhood, is generally asymptomatic; however EBV infection may cause infectious mononucleosis when acquired in adolescence or adulthood. EBV persists for life in the memory B cells compartment and reactivation of EBV is prevented by an effective immunosurveillance mediated through virus-specific T-cell immunity [5]. However, infected B cells can proliferate without control in the absence of an effective immune response, resulting in malignant transformation. This process is exemplified by the development PTLD or lymphoproliferative disorders in patients undergoing immunosuppressive therapy for other medical conditions [6,7]. Currently, reactivation of EBV is an increasing complication in immune deficient patients, particularly after HSCT or SOT [7]. Whereas the tapering of immunosuppression, donor lymphocyte infusion, and rituximab may be effective for this complication after HSCT, severe adverse events such as fatal graft-versus-host disease and infections could develop thereafter [8,9], therefore effective but less toxic anti-EBV therapies are needed.Resveratrol Prevents EBV-Transformation of B CellsResveratrol (3, 49, 5 tri-hydroxystilbene) is a naturally occurring polyphenol found in red wine, grapes and other sources [10]. Numerous health benefits have been associated with resveratrol including anti-inflammatory, anti-aging and antitumor activities [10,11]. The broad anti-cancer activities of resveratrol are exerted by a particular property of this compound to target multiple proteins including the NFkB, STAT-3, and AKT pathways which are all involved in the regulation of cell proliferation, survival and apoptosis [11?3]. Several studies have reported inhibitory activities of resveratrol against various virus including herpes simplex virus 1 and 2, Varicella zoster virus, human cytomegalovirus, and influenza virus, however, the mechanisms for such antiviral properties have not been clearly defined [14,15]. The current study investigated the potential antiviral effects of resveratrol against EBV, and focused on the modulation of the oncogenic properties of this virus. This study took advantage of the ability of EBV to transform B cells into lymphoblastoid cell lines (LCL) in vitro, which recapitulates many aspect of the EBV-related malignant transformation. The data revealed that resveratrol effectively prevented the EBV-induced transformation of B cells, which was mediated by the inhibitory effects of resveratrol on multiple genes involved in transformation and survival of human B cells. This is the first report to show mechanistic insights into the efficacy of resveratrol to pr.