EBV latent life cycle. Virus enters though mucosal routes (shown is the buccal cavity), then infects normal naive B cells circulating through mucosal sites. Virus expresses type 3 latency, which drives B-cell proliferation and expands the infected memory pool. B-cell differentiation into the memory compartments occurs in germinal centers driven by type 2 latency proteins. Infected memory B cells exiting the germinal center down-regulate viral proteins and are invisible to the immune response. EBNA1 is expressed during homeostatic proliferation to maintain the latent viral episome. Virus replication is induced at mucosal sites, and virus is released into the saliva. PTLD indicates posttransplantation lymphoproliferative disease; HD, Hodgkin disease; NPC, nasopharyngeal cancer, and BL, Burkitt lymphoma.