Abstract
During the course of simian immunodeficiency virus (SIV) infection, nearly 15% of rhesus macaques (Macaca mulatta) and up to 40% of cynomolgus macaques (Macaca fascicularis) developed SIV‐associated non‐Hodgkin's lymphomas. Most of these malignant lymphomas harbored lymphocryptoviruses, which are closely related to the human Epstein‐Barr virus (EBV; Herpesvirus M. mulatta and Herpesvirus M. fascicularis). To characterize the oncogenic role of simian EBV infection for lymphomagenesis during SIV infection, expression of the EBV‐encoded latent membrane protein‐1 (LMP‐1) was analyzed in malignant lymphomas of SIV‐infected rhesus macaques. Nine seropositive rhesus macaques suffering from B‐cell lymphomas during the late phase of SIV infection were euthanized. Latency stages of EBV infection within malignant lymphomas and simian EBV‐infected lymphoblastoid cell lines (LCL8664, H50) were characterized by analyzing expression of the EBV‐encoded nuclear antigens EBNA‐1, EBNA‐2, and small RNAs EBER1/2. In parallel, the presence of viral LMP‐1 transcripts was assessed by reverse transcription‐polymerase chain reaction (RT‐PCR) and in situ hybridization. Results were compared with findings in AIDS‐associated malignant lymphomas in two patients infected with human immunodeficiency virus (HIV)‐1. Rhesus macaques developed high‐grade B‐cell lymphomas of the centroblastic (five of nine), immunoblastic (two of nine), centroblastic‐centrocytic (one of nine), and Burkitt‐like (one of nine) subtypes within 18–29 months postinfection with SIV~mac~251/32H. The presence of Herpesvirus M. mulatta was detected in eight of nine cases. Transcription of the viral oncogene LMP‐1 could be demonstrated within the simian EBV‐infected cell lines as well as in four of nine SIV‐associated malignant lymphomas. These four cases and both of the HIV‐1–related non‐Hodgkin's lymphomas expressed the full spectrum of latent EBV gene products (LMP‐1, EBER1/2, EBNA‐1, EBNA‐2) and were thus classified as latency type III stages of EBV infection. Simian EBV infection was demonstrated in 90% of lymphomas in SIV‐infected rhesus macaques. Analysis of LMP‐1 expression suggests an important role for this viral oncogene in the pathogenesis of both SIV and HIV‐1–associated malignant lymphomas. J. Med. Virol. 65:114–120, 2001. © 2001 Wiley‐Liss, Inc.