Activation of B virus (Herpesvirus simiae) in chronically immunosuppressed cynomolgus monkeys

Three of 14 cynomolgus monkeys given the highest dose of an immunosuppressive drug in a 6-month toxicology study developed B virus (Herpesvirus simiae) oral lesions after 3 months of dosing. This necessitated early removal of all high-dose monkeys from the study due to concerns related to B virus. The incidence and severity of parasitic (Oesphagostomum sp.) lesions of the large intestine were also increased in high-dose animals. Both B virus and Oesophagostomum are enzootic in macaques, and the lesions caused by them were considered secondary to chronic immunosuppression caused by the highest dose of the test compound. Evidence of immunosuppression included decreased lymphocyte counts (B-cells; CD2 and CD8 T-cells), histopathologic evidence of lymphoid suppression, and serum-induced inhibition of lymphocyte mitogen responses. Pathogenesis of the B virus was apparently associated with both activation of latent virus as well as transmission of active virus. Approaches for virologic monitoring of primates and for ensuring optimal safety for primate handlers are discussed.