Figure 1.

Schematic drawing of our model of EBV persistence. During acute infection, EBV transmitted via saliva infects naive B cells turning them into latently infected B-cell blasts (bB_Lats) and driving their proliferation and differentiation through a germinal center (gcB_Lat) into latently infected memory B cells (mB_Lats) that then migrate to peripheral blood where EBV persists for the lifetime of its host. When mB_Lats migrate back to the tonsil, they occasionally receive signals to undergo terminal differentiation into plasma B cells, which triggers reactivation of the virus. This results in the subsequent expression of lytic genes (eg, IE and EA) and ultimately production of free virions that can then infect new B cells or shed into saliva to infect new hosts. This process in turn stimulates an aggressive antiviral CTL response. The infected cells expressing targets recognized by CTLs are indicated. This response effectively reduces the number of cells that complete viral replication so that during persistent infection little or no new infection of B cells occurs. Whether the stable levels of mB_Lats during persistence are maintained through memory B-cell homeostasis, low-level infection of new B cells, or a combination of the 2 is unresolved.