Induction of B cell hyperplasia in simian immunodeficiency virus-infected rhesus macaques with the simian homologue of Kaposi's sarcoma-associated herpesvirus

A simian homologue of Kaposi's sarcoma-associated herpesvirus (KSHV), the e ighth human herpesvirus (HHV8), was isolated from a simian immunodeficiency virus (SIV)-infected rhesus macaque (Macaca mulatta) that developed a mult icentric lymphoproliferative disorder (LPD). This simian rhadinovirus is ge netically similar to a recently described rhesus rhadinovirus (RRV) (Desros iers, R.C., V.G. Sasseville, S.C. Czajak, X. Zhang, K.G. Mansfield, A. Kaur , R.P. Johnson, A.A. Lackner, and J.U. Jung. 1997. J Virol. 71:9764-9769) a nd is designated RRV 17577. RRV 17577 was experimentally inoculated into rh esus macaques with and without SIVmac239 infection to determine if RRV play ed a role in development of the LPD observed in the index case. In contrast to control animals inoculated with SIVmac239 or RRV alone, two animals coi nfected with SIVmac239 and RRV 17577 developed hyperplastic LPD resembling the multicentric plasma cell variant of Castleman's disease, characterized by persistent angiofollicular lymphadenopathy, hepatomegaly, splenomegaly, and hypergammaglobulinemia. Hypergammaglobulinemia was associated with seve re immune-mediated hemolytic anemia in one RRV/SIV-infected macaque. Both R RV/SIV-infected macaques exhibited persistent RRV viremia with little or no RRV-specific antibody response. The macaques inoculated with RRV alone dis played transient viremia followed by a vigorous anti-RRV antibody response and lacked evidence of LPD in peripheral blood and lymph nodes. Infectious RRV and RRV DNA were present in hyperplastic lymphoid tissues of the RRV/SI V-infected macaques, suggesting that lymphoid hyperplasia is associated wit h the high levels of replication. Thus, experimental RRV 17577 infection of SIV-infected rhesus macaques induces some of the hyperplastic B cell LPDs manifested in AIDS patients coinfected with KSHV.