Elevated secretion of inflammatory factors is associated with latent Epstein-Barr virus (EBV) infection and the pathology of EBV-asso-
Infection by the Epstein-Barr virus (EBV) causes infectious mononucleosis and several malignant cancers, including Burkitt's lymphoma, Hodgkin's lymphoma, nasopharyngeal carcinoma (NPC), and gastric carcinoma, as well as posttransplant lymphomas (1-5). EBV infection is persistent worldwide, but the frequency of EBV-associated NPC is highest in southern China, while Burkitt's lymphoma is most commonly found in equatorial Africa (2, 3). Although the exact mechanism by which EBV causes tumorigenesis remains to be fully defined, two important cofactors are strongly involved in EBV pathogenesis: genetic susceptibility and local diet. Unique polymorphisms of NPC-associated EBV have been identified in Chinese individuals, indicating the existence of EBV variants with higher pathogenic potential for NPC than that seen in the typical Western strains that cause infectious mononucleosis (6-8).Latent infection with limited gene expression is the default EBV cycle, whereas the lytic cycle is essential for transmission (1, 9). Lytic replication during primary infection or reactivation from the latent cycle is initiated by the expression of the immediate early (IE) viral transactivators BZLF1 and BRLF1. BZLF1, an EBV-encoded transcription factor of the basic-leucine zipper (b-ZIP) family, activates both viral and cellular genes by binding to BZLF1-responsive elements (ZREs), including several transcription factors and inflammatory factors (10).Inflammatory mediators have complex roles in cancer and infectious diseases, either limiting or promoting these disorders (11-15). Several proinflammatory factors have been fully characterized in experimental and clinical studies, including tumor necrosis factor alpha (TNF-␣), interferon gamma (IFN-␥), interleukin-1␣ (IL-1␣), and IL-1. TNF-␣ serves as an antiviral immune factor operating via two different mechanisms: induction of apoptosis in infected cells and activation of the antiviral response in uninfected cells (16)(17)(18)(19). For successful infection and replication, viruses employ multiple strategies to escape or hijack the host defenses, including innate immunity and the inflammatory response (15,17,20). The EBV lytic cycle evades the host inflammatory responses through the activity of BZLF1, which inhibits both IFN-␥ signaling and tumor necrosis factor receptor 1 (TNFR1) signaling (21-23). BZLF1 suppresses the NF-B signaling pathway by directly binding the p65 subunit (24, 25), acting as an
