Innate immune modulation in EBV infection

Epstein-Barr Virus (EBV), known as human herpesvirus 4 (HHV4), is the first identified human cancer virus that has been shown to be associated with the development of a wide spectrum of B-cell lymphoproliferative disorders including Burkitt's lymphoma (BL), Posttransplant lymphoproliferative disorder (PTLD), and Hodgkin and non-Hodgkin lymphomas, as well as epithelial cancers including Nasopharyngeal carcinoma (NPC) and some forms of gastric carcinoma [1]. EBV is also associated with lymphomas occurring in rare patients with congenital immunodeficiency such as X-linked lymphoproliferative syndrome (XLP) [2], and plays a role in lymphoproliferative disorders which most often occur in immunocompromised patients with human immunodeficiency virus (HIV) infection (e.g. central nervous system lymphoma) or after solid organ transplantation. EBV, together with Kaposi's sarcoma-associated herpesvirus (KSHV/HHV8) and human papillomavirus (HPV), are three oncogenic viruses causally involved in acquired immune deficiency syndrome (AIDS)-associated malignancies [3].Herpesviruses are fascinating models for scientific research as they establish lifelong persistent infections in normal immunocompetent healthy hosts as well as are able to be reactivated (replicate) for spreading to new hosts. Human herpesviruses are of particularly medical importance because they are associated with severe diseases and cancers in immunocompromised hosts [4]. Among herpesviruses, EBV is a well-established paradigm for the study of herpes viral infection, persistence, and associated malignancies [4].EBV is spread by saliva contact, and then crosses mucosal epithelium in order to infect B cells in underlying secondary lymphoid tissues like the tonsils and adenoids. Besides spread by saliva contact, EBV may be sexually transmitted [5]. Breast milk of nursing mothers may also contain EBV which could be from an uncommon route of vertical transmission [6]. In healthy hosts, the immune system forces invadin