Intensive immune suppression of Bolivian squirrel monkeys activates latent polyomavirus (HUM8P.337)

The squirrel monkey polyomavirus (SMPyV) is commonly found in Bolivian squirrel monkeys, and, as such, the squirrel monkey may be a useful model for the study of polyomavirus-associated pathogenesis and experimental treatment and prevention strategies. Squirrel monkeys were given single or multiple doses of an anti-B cell antibody (Rituximab) and/or an anti-CD8 monoclonal antibody (7pt-3F9) which resulted in a complete CD20+lymphocyte depletion and transient CD8+lymphocyte depletion as compared to control animals. The animals remained clinically well, suggesting that the intensity and/or duration of immune suppression were inadequate to trigger pathogenic reactivation of the latent polyoma and herpes viruses. Quantitative PCR assays revealed excretion of the SMPyV in the urine within one week after the 7pt-3F9 infusion, continuing until the end of the study. At necropsy, spleen, liver, lymph nodes, cerebrum, cerebellum and kidney were positive for SMPyV DNA. Histologic and immunohistochemistry studies revealed moderately increased numbers of meningeal cells and inflammatory mononuclear cells in the kidney, renal medulla and foci of increased Ki67 staining in distal tubular epithelial cells in antibody treated monkeys compared to untreated monkey. One animal had multifocal encephalitis with prominent CD3+lymphocyte collections throughout the cortex. These results suggest that the transient depletion of CD8+lymphocytes may be a useful trigger for SMPyV shedding.