Latent simian varicella virus reactivates in monkeys treated with tacrolimus with or without exposure to irradiation

Simian vancella virus (SVV) infection of primates resembles human varicella-zoster virus (VZV) infection After primary infection, SVV becomes latent in ganglia and reactivates after immunosuppression or social and environmental stress Herein, natural SVV infection was established in 5 cynomolgus macaques (cynos) and 10 African green (AG) monkeys Four cynos were treated with the immunosuppressant tacrolimus (80 to 300 mu g/kg/day) for 4 months and 1 was untreated (group 1) Four AG monkeys were exposed to a single dose (200 cGy) of x-irradiation (group 2), and 4 other AG monkeys were irradiated and treated with tacrolimus for 4 months (group 3), the remaining 2 AG monkeys were untreated Zoster rash developed 1 to 2 weeks after tacrolimus treatment m 3 of 4 monkeys m group 1, 6 weeks after irradiation in 1 of 4 monkeys in group 2, and 1 to 2 weeks after irradiation m all 4 monkeys in group 3 All monkeys were euthanized 1 to 4 months after immunosup pression SVV antigens were detected immunohistochemically in skin biopsies as well as in lungs of most monkeys Low copy number SVV DNA was detected in ganglia from all three groups of monkeys, including controls RNA specific for SVV ORFs 61, 63, and 9 was detected in ganglia from one immunosuppressed monkey in group 1 SVV antigens were detected m multiple ganglia from all immunosuppressed monkeys m every group, but not in controls These results indicate that tacrolimus treatment produced reactivation m more monkeys than irradiation and tacrolimus and irradiation increased the frequency of SVV reactivation as compared to either treatment alone Journal of Neuro Virology (2010) 16, 342-354