Epstein-Barr virus (EBV) is a human lymphocryptovirus that causes infe
ctious mononucleosis, persists asymptomatically for life in nearly all
adults, and is associated with the development of B cell lymphomas an
d nasopharyngeal carcinomas. A highly similar rhesus lymphocryptovirus
naturally endemic in rhesus monkeys was used to orally inject naive a
nimals from a pathogen-free colony. This animal model reproduced key a
spects of human EBV injection, including oral transmission, atypical l
ymphocytosis, lymphadenopathy, activation of CD23(+) peripheral blood
B cells, sustained serologic responses to lytic and latent EBV antigen
s, latent infection in the peripheral blood, and virus persistence in
oropharyngeal secretions. This system may be useful for studying the p
athogenesis, prevention, and treatment of EBV infection and associated
oncogenesis.