A Monkey Model for Epstein Barr Virus-associated Lymphomagenesis in Human Acquired Immunodeficiency Syndrome

Abstract

High-grade malignant nonHodgkin's lymphomas-five lymphoblastic, three pleomorphic, and two immunoblastic-developed in 10/25 cynomolgus monkeys (Macacafascicularis) followed for up to 746 d after infection with simian immunodeficiency virus, strain SIVsm. These lymphomas were shown to be associated with an Epstein-Barr (EB)-like cynomolgus B-lymphotropic herpesvirus (CBLV) by electron microscopy, by Southern blot hybridization with probes against human EBV, and by the expression of antigens corresponding to EBV-associated nuclear antigens (EBNAs) involved in human B cell transformation. Southern blot demonstration ofimmunoglobulin gene rearrangements and homogeneous EBV episomes indicated that all the lymphomas were CBLVassociated monoclonal B cell proliferations. Our findings suggest that these tumors correspond to the EBV-associated malignant lymphomas in acquired immunodeficiency syndrome with respect to clinical, morphological, phenotypic, and genotypic characteristics. The particular susceptibility of SIVsm immunodeficient cynomolgus monkeys for CBLV-associated lymphomagenesis appears therefore a useful model for EBV-associated lymphomas in humans.