The Journal of Experimental Medicine
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© The Rockefeller University Press, 0022-1007/1999/9/827/ $5.00
The Journal of Experimental Medicine, Volume 190, Number 6, September 20, 1999 827-840

Original Article

Induction of B Cell Hyperplasia in Simian Immunodeficiency Virus–Infected Rhesus Macaques with the Simian Homologue of Kaposi's Sarcoma–Associated Herpesvirus

Scott W. Wonga,c, Eric P. Bergquama, Ryan M. Swansona, Felix W. Leea, Stanley M. Shiigia, Nancy A. Averya, John W. Fantonb, and Michael K. Axthelma

a Division of Pathobiology and Immunology, Oregon Regional Primate Research Center, Beaverton, Oregon 97006
b Division of Animal Resources, Oregon Regional Primate Research Center, Beaverton, Oregon 97006
c Department of Molecular Microbiology and Immunology, Oregon Health Sciences University, Portland, Oregon 97201
Division of Pathobiology and Immunology, Oregon Regional Primate Research Center, 505 NW 185th Ave., Beaverton, OR 97006.503-690-5524503-690-5285

wongs{at}ohsu.edu

A simian homologue of Kaposi's sarcoma–associated herpesvirus (KSHV), the eighth human herpesvirus (HHV8), was isolated from a simian immunodeficiency virus (SIV)-infected rhesus macaque (Macaca mulatta) that developed a multicentric lymphoproliferative disorder (LPD). This simian rhadinovirus is genetically similar to a recently described rhesus rhadinovirus (RRV) (Desrosiers, 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) and is designated RRV 17577. RRV 17577 was experimentally inoculated into rhesus macaques with and without SIVmac239 infection to determine if RRV played 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 coinfected 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 severe immune-mediated hemolytic anemia in one RRV/SIV-infected macaque. Both RRV/SIV-infected macaques exhibited persistent RRV viremia with little or no RRV-specific antibody response. The macaques inoculated with RRV alone displayed 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/SIV-infected macaques, suggesting that lymphoid hyperplasia is associated with 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.

Key Words: B cell hyperplasia • simian immunodeficiency virus • rhesus rhadinovirus • lymphoproliferative disorders • nonhuman primate

1used in this paper: BM, bone marrow; CPE, cytopathic effects; EBV, Epstein-Barr virus; HVS, Herpesvirus saimiri; KS, Kaposi's sarcoma; KSHV, KS-associated herpesvirus; LMP, latent membrane protein; LPDs, lymphoproliferative disorders; MCD, multicentric Castleman's disease; MIP, macrophage inflammatory protein; orfs, open reading frames; PEL, primary effusion lymphoma; RRV, rhesus rhadinovirus; SIV, simian immunodeficiency virus; TS, thymidylate synthase

© 1999 The Rockefeller University Press


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