Cyclophosphamide effects on latent herpesvirus in adult dogs

Abstract

Latent canine herpesvirus-1 (CHV-1) infection is common in domestic dogs, but triggers for viral reactivation and recrudescent CHV-1 disease are poorly understood. Cyclophosphamide is a potent immunosuppressive and myelosuppressive agent used for the therapy of a variety of neoplastic and immune-mediated canine disorders. Cyclophosphamide (200mg/m(2)) was administered to mature dogs latently infected with CHV-1 to determine its potential to induce recurrent CHV-1 disease and viral shedding. Non-infected dogs and dogs recovered from experimental primary ocular CHV-1 infection with experimentally confirmed latent CHV-1 infection were divided into groups and administered cyclophosphamide or placebo. Dogs were monitored for myelosuppression and viral reactivation for 28days using clinical and virological outcome measures. Clinical ophthalmic and in vivo ocular confocal microscopic examinations were performed at intervals. Samples were collected for CHV-1 polymerase chain reaction (PCR), CHV-1 virus neutralizing (VN) antibody, and hemogram assays. Myelosuppression (i.e., decreased total leukocyte, segmented neutrophil, and erythrocyte counts) was detected on study day 7 in dogs administered cyclophosphamide, but not dogs administered placebo. There were no abnormalities suggestive of recurrent CHV-1 ocular disease during clinical ophthalmic or in vivo confocal microscopic examination in any dogs during the study. Ocular CHV-1 shedding was not detected by PCR and CHV-1 VN titers remained stable in all dogs. Following study conclusion, the presence of reactivatable latency was reconfirmed in the infected dogs by administering systemic prednisolone. Myelosuppression elicited by a single dose of cyclophosphamide does not result in detectable recurrent ocular CHV-1 infection in adult dogs with experimentally induced latent CHV-1 infection.