Important note: Information in this article was accurate in 1994. The state of the art may have changed since the publication date.
B-cell lymphomagenesis in SIV immunosuppressed cynomolgus monkeys.
Symp Nonhum Primate Models AIDS. 1993 Sep 19-22;11:abstract no. 46. Unique Identifier : AIDSLINE PRIM11/94191641 Biberfeld P; Kaaya EE; Feichtinger H; Li SL; Ekman M; Ernberg I; Voevodin AF; Putkonen P; Biberfeld G; Immunopathology Lab., Karolinska Institute, Stockholm, Sweden.
Abstract:
OBJECTIVE: To characterize lymphomagenic mechanisms in SIV immunosuppressed cynomolgus monkeys (Macaca fascicularis). MATERIAL AND METHODS: Monkeys immunosuppressed by SIVsm (SMM3) developed malignant lymphoma in high frequency (approx. 40%). These lymphomas were studied by immunohistopathology, anticomplement immunofluorescence (ACIF), Western blot (WB), polymerase chain reaction (PCR), Southern blot (SB), in situ hybridization, electron microscopy and cell culture. RESULTS AND CONCLUSIONS. Lymphoma induction time varied from 5 to 46 months. All monkeys with lymphoma were markedly immunosuppressed. Most lymphomas were primarily extranodal including CNS, of high-grade malignant histology, of B-cell origin and associated with a B-lymphotropic herpes virus apparently closely related to human EBV (EBRVmf) by SB and PCR. using EBV-specific DNA-probes and primers respectively. By in situ hybridization an EBER-RNA equivalent was demonstrated in sections and cultures of the lymphomas. A pathogenic role of the EBRVmf was indicated by the presence of nuclear antigens (CYNA) in lymphoma cells both on sections and in established cell lines, which showed reactivity for antibodies to human EBNA-1 (CYNA-1) and EBNA-2 (CYNA-2) and bands of 50kd and 100kd in WB respectively. In cultured lymphoma cells 3-5% of the cells showed replication (factories) of a virus with the characteristic ultrastructure of a herpes virus (EBV). The immune phenotype of these monkey lymphomas resembles that of EBV-infected LCL's found in human AIDS lymphomas. These observations indicate a marked similarity of lymphomas in SIV immunosuppressed monkeys with human AIDS-lymphomas associated with EBV.
Keywords: Animal Antigens, Viral/ANALYSIS Blotting, Southern Blotting, Western Comparative Study DNA Primers DNA Probes DNA-Binding Proteins/ANALYSIS Fluorescent Antibody Technique Herpesvirus 4, Human/IMMUNOLOGY/ISOLATION & PURIF Human In Situ Hybridization Lymphoma, AIDS-Related/PATHOLOGY Lymphoma, B-Cell/EPIDEMIOLOGY/*ETIOLOGY/IMMUNOLOGY/PATHOLOGY Macaca fascicularis Polymerase Chain Reaction Simian Acquired Immunodeficiency Syndrome/COMPLICATIONS/ *IMMUNOLOGY Support, Non-U.S. Gov't *SIV Time Factors Tumor Cells, Cultured ABSTRACT
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