Epstein-Barr virus (EBV), also designated human herpesvirus 4 (HHV4), is oneof eight human herpesviruses that establish latent infections in human hosts(reviewed in Pellett and Roizman 2007). Herpesviruses are organized into threesubfamilies (α,β,γ) depending on biological characteristics and evolutionaryrelatedness. All share many similar properties including the ability to enter hostcells via a multistep process that culminates with the fusion of the virionenvelope with a host membrane releasing the capsid into the cytoplasm toinitiate virus infection. There are two γ-herpesvirus that infect humans-EBVand the recently identifiedHHV8. Research on EBV has considerably expandedsince its discovery and link with Burkitts lymphoma (Burkitt 1962; Epsteinet al. 1964). Along with HHV8, EBV is the only herpesvirus with an etiologicalrole in human malignancies. It is almost universally found in endemic Burkittslymphoma and undifferentiated nasopharyngeal carcinoma and is an importantpathogen in individuals lacking cellular immunity from genetic defects,immune suppression for organ transplantation, or HIV infection (reviewed inRickinson and Kieff 2007). In immunosuppressed patients, EBV causes avariety of proliferative disorders including immunoblastic lymphomas, oralhairy leukoplakia, and an unusual tumor of muscle origin in children. It hasalso been linked to variety of other human cancers including some T-celllymphomas, Hodgkins disease, and gastric carcinoma (reviewed in Rickinsonand Kieff 2007). Infection with EBV usually occurs early in childhood resultingin a disease that is not typically recognized as a clinical entity. If primaryinfection occurs in adolescence or later, B-cell proliferation and the resultingimmune response more commonly results in infectious mononucleosis. Afterprimary infection, most individuals harbor the virus for life and develop cellularimmunity against a variety of viral antigens (for review (Rickinson and Kieff2007)). Periodically, virus is shed from latently infected individuals by theinduction of lytic replication in B lymphocytes. Overall, the pathologies associatedwith EBV infection suggest that the two primary cell types that EBVinfects in vivo are epithelial cells and B lymphocytes.
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