Expression of epstein‐barr‐virus‐related nuclear antigens and B‐cell markers in lymphomas of SIV‐immunosuppressed monkeys

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Abstract
Simian-immunodeficiency-virus(SIV)-infected cynomolgus monkeys develop B-cell lymphomas in approximately one third of the cases. We have now studied the expression of cynomolgus-Epstein-Barr-virus(cyno-EBV) nuclear antigens in 13 cyno-EBV-carrying SIVsm-associated monkey lymphomas and established cell lines from 3 of these tumors. Immunoblots of cell lysates were probed with polyspecific and monospecific reagents directed against human EB-virus EBNA1-6, and against the membrane protein LMP1. An EBNA2-cross-reacting protein was demonstrated in 8 lymphoma tissues (8/13) and in the 3 cell lines derived from the tumors. All tumors expressed a polypeptide with 50 to 55 kDa molecular weight, which cross-reacted with some antibodies to EBNA1. Absorption experiments with normal monkey tissue showed that this polypeptide was specific for the cyno-EBV-carrying lymphoma cells. Equivalents of EBNA3-6 and LMP1 could not be detected. Immunophenotypical characterization showed that the monkey lymphomas were similar to human HIV-associated B-cell lymphomas. Malignant B-cell lymphomas in experimentally SIVsm-infected cynomolgus monkeys can be a model for EBV-associated lymphomagenesis in immunodeficiency states. This study was supported by grants from the Swedish Medical Research Council, the Swedish Cancer Society and Erik and Edith Fernström's Foundation for Medical Research. We thank Dr. J. Dillner (Department of Virology, Karolinska Institute) for helpful suggestions, Ms. A. de Santiago de Aguilar, Ms. M. Ekman and Ms. R. Gendelman for skillful technical assistance, and Drs. A. Rickinson and M. Rowe, CRC laboratories, for PE-2 MAb. H. F. was partly supported as a visiting scientist by the European Community Concerted Action “Pathophysiology and immunology of HIV-related diseases”, and E.K. (visiting scientist from Muhimbili Medical Centre, Dar-es-Salaam, Tanzania) was supported by the Swedish Agency for Research Cooperation with Developing Countries (SAREC) and World Laboratory (Project MDC 2).

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