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Epstein-Barr virus (EBV) infects most people worldwide and persists for life due to complicated interplay between lytic infection and multiple types of latent infections. While usually asymptomatic, EBV is a causative agent in several types of cancer and has a strong association with multiple sclerosis. Exactly how EBV promotes these diseases and why they are rare consequences of infection are incompletely understood. Here I will discuss current ideas on disease induction by EBV, including the importance of lytic protein expression in the context of latent infection as well as the possible importance of specific EBV variants in disease induction.