Exogenous but not endogenous EBV induces lymphomas in beige/nude/xid mice carrying human lymphoid xenografts

Abstract
Epstein-Barr virus (EBV) is a latent human herpes virus that growth-transforms EBV receptor/CD21 +B cells and Is associated with several high-frequency malignancies. Reactivation of latent EBV occurs in -1/3 of organ graph recipients and a majority of AIDS patients; EBV-positive B lymphoproliferative lesions represent often fatal complications in organ transplantation and late-stage AIDS. Although such lymphomas can arise from endogenous virus, the hightumor risk in EBV-seronegative transplant recipients implies de novo infection, In particular virus transmission with intra-graft B lymphocytes. Since SCID mice engrafted with human lymphocytes (SCIDhum) typically develop endogenous EBV+ (human) tumors in their graft it is difficult to study exogenous virus transmission In this model. We here demonstrate that belge/nude/xid mice engrafted with human lymphoid cells (BNXhum) selectively accept human B but not T cell grafts. Unexpectedly these mice fall to develop endogenous lymphomas observed in SCIDhum mice engrafted in parallel. However, injection of as few as hum animals. This virus sensitivity of BNXhum approaches conditions for EBV transmissionwith organ grafts.

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