| Non-Hodgkin's lymphomas occur with increased frequency (3--6%) in HIV-infected individuals. These AIDS-associated lymphomas (AALs) exhibit distinct characteristics which have allowed investigators to propose a model for their development. Verification of the model would be facilitated by testing in an animal model system. Since 1984 at the Tulane Regional Primate Research Center, necropsy examinations of more than 1000 SIV-infected macaques have been performed, and lymphoid malignancies were detected in 38 animals. These SAIDS-associated lymphomas (SAL) have been studied to determine the extent to which they recapitulate the primary pathobiological features of AAL, and whether or not rhesus lymphocryptovirus (RhLCV), a rhesus homologue of EBV, plays a pathogenic role in the malignant process. The results show that lymphomas occur in SIV-infected rhesus macaques at 4% incidence, similar to that of AAL, and that the incidence of SAL in SIV-infected cynomolgus macaques is eight-fold higher. SAL represents a monoclonal expansion of B-cell origin in which SIV is not detected. Using PCR and/or in situ hybridization, we determined the incidence of RhLCV infection in SAL from rhesus macaques to be 89%. Twenty-five percent of SAL from cynomolgus macaques are infected with a cynomolgus homologue of EBV. The second objective was addressed by studying whether the level of RhLCV infection in SIV-infected macaques is influenced as a function of disease progression, and/or whether increased levels of RhLCV infection may correlate with the development of SAL. To this end, RhLCV infection was evaluated in three independent groups by PCR/Southern blot analysis, visual comparison to a standard dilution series, and assignment of relative signal intensity to a uniform classification scheme. The data show that SIV-infected monkeys have a generally higher RhLCV load in PBMC than do healthy animals, but the virus load varies widely among animals during disease progression. Increased RhLCV load does not occur uniformly during the progression of SAIDS, although evidence indicates an increased RhLCV viral load in the development of SAL. Additionally, RT-PCR revealed that 13/13 SAL cases expressed EBNA-2 and LMP-1, RhLCV immortalizing genes. These findings overall indicate that lymphoma in the HIV-infected human and the SIV-infected macaque share a common pathobiology. |
