The pathogenesis of Epstein–Barr virus persistent infection

• We summarize and update the germinal center model of Epstein–Barr virus persistence.
• We discuss the weaknesses and strengths of alternate models.
• The role of LMP1 and LMP2 in the germinal center process needs further study.
• The role of EBV-infected GC B cells in lymphomagenesis needs to be understood.
• Mathematical modeling has provided fresh insights into EBV persistence.

Epstein–Barr virus (EBV) maintains a lifelong infection. According to the germinal center model (GCM), latently infected B cells transit the germinal center (GC) to become resting memory cells. Here, the virus resides quiescently, occasionally reactivating to infect new B cells, completing the cycle of infection. The GCM remains the only model that explains EBV biology and the pathogenesis of lymphoma. Recent work suggests modifications to the model notably that the virus contributes only modestly to the GC process and predictions from mathematical models that quiescence within memory B cells shapes the overall structure of viral infection but is not essential for persistence. Rather, it is the cycle of infection which allows viral persistence at the very low levels observed.