SIV
infection of macaques is a well-established animal model for studying the pathogenesis of
HIV infection in humans. During the course of SIV
infection, up to 40% of cynomolgus macaques (Macaca fascicularis) develop SIV-associated non-Hodgkin's
lymphomas. In the present study, we characterized
malignant lymphomas of SIV(mac) 251/32H-infected rhesus macaques (Macaca mulatto) of our cohort in terms of clinical outcome, histopathology and EBV association. Histopathologic changes of lymphoid
malignancies were classified according to the Kiel classification. For detection of the EBV-encoded small RNAs
EBER1 and
EBER2, a method of non-isotopic in situ hybridization was established. The presence of EBNA-2
antigens was assessed by immunohistochemistry. Seven of 43 rhesus macaques developed highly malignant
B-cell lymphomas of the centroblastic, immunoblastic and Burkitt subtypes within 18-29 months post-experimental SIV
infection. In situ hybridization revealed the presence of small
EBER1 and -2 RNAs in 6 of 7 disease cases. EBNA-2
antigens could be demonstrated in only 4 of 7 tissue specimens. As expected, the Burkitt-type of
lymphoma was negative for EBNA-2
antigen staining. In accordance with findings on SIV-associated
lymphomas of cynomolgus macaques,
infection with an EBV-related herpesvirus could be demonstrated in almost 90% of
lymphomas in SIV-infected rhesus macaques. In contrast, the presence of EBV in
lymphomas had been documented previously in only 30-40% of HIV-infected patients. Further studies should thus define the precise role of
herpesvirus infection for lymphomagenesis in SIV- and HIV-induced immunodeficiency.