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Viral interleukin-6 encoded by rhesus macaque rhadinovirus is associated with lymphoproliferative disorder (LPD)
Authors:B.U. Orzechowska,M. Manoharan,J. Sprague,R.D. Estep,M.K. Axthelm,&   S.W. Wong
Affiliation: Vaccine and Gene Therapy Institute, Oregon Health &Science University, West Campus, Beaverton, OR, USA;
 Division of Pathobiology and Immunology, Oregon National Primate Research Center, Beaverton, OR, USA;
 Department of Molecular Microbiology and Immunology, Oregon Health &Science University, Portland, OR, USA
Abstract:Background  Rhesus macaques (RM) co-infected with simian immunodeficiency virus (SIV) and rhesus macaque rhadinovirus (RRV) develop abnormal cellular proliferations characterized as extra-nodal lymphoma and retroperitoneal fibromatosis (RF). RRV encodes a viral interleukin-6 (vIL-6), much like Kaposi's sarcoma-associated herpesvirus, and involvement of the viral cytokine was examined in proliferative lesions.
Methods  Formalin fixed tissue from RM co-infected with SIV and RRV were analyzed for RRV genomes by in situ hybridization and RRV vIL-6 expression by immunofluorescence analysis.
Results  In situ hybridization analysis indicated that RRV is present in both types of lesions. Immunofluorescence analysis of different lymphomas and RF revealed positive staining for vIL-6. Similarly to KS, RF lesion is positive for vimentin, CD117 (c-kit), and smooth muscle actin (SMA) and contains T cell, B cell and monocytes/macrophage infiltrates.
Conclusions  Our data support the idea that vIL-6 may be critical to the development and progression of lymphoproliferative disorder in RRV/SIV-infected RM.
Keywords:multi-centric Castleman's disease    neoplasia    RRV and SIV
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