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An animal model for Epstein–Barr virus (EBV)‐associated lymphomagenesis in the human: Malignant lymphoma induction of rabbits by EBV‐related herpesvirus from cynomolgus

It is very important to develop and analyze animal models of Epstein–Barr virus (EBV)‐associated tumors in the human. However, only a few reports on the animal models of EBV infection have been reported. Here we review those previous models and describe the details on our newly developed rabbit model of malignant lymphoma induced by EBV‐related virus from cynomolgus. In brief, Si‐IIA‐EBV or Cyno‐EBV induced T‐cell lymphomas in rabbits inoculated intravenously (77–90%), orally (82–89%), subcutaneously (3/3) and intraperitoneally (2/3) about 2–5 months later. EBV‐DNA was detected in peripheral blood by polymerase chain reaction 2 days after oral inoculation of Cyno‐EBV while antiviral capsid antigen immunoglobulin G (IgG) was raised 3 weeks after the inoculation. Rabbit lymphomas and their cell lines contained EBV‐DNA and expressed EBV‐encoded small RNA‐1 and EBV‐associated nuclear antigen. Rabbit lymphoma cell lines, some of which have specific chromosomal abnormality, showed tumorigenicity in nude mice. The significance and further research subjects of this animal model will be discussed. We believe that the present rabbit model of lymphoma with specific chromosomal abnormalities is very useful for clarifying the role of EBV in human EBV‐associated lymphoma and provides a means for studying prophylactic and therapeutic regimens.