SIMIAN VARICELLA VIRUS INFECTION AND LATENCY IN THE NONHUMAN PRIMATE

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Simian varicella virus (SVV) infection of primates shares clinical, pathological, immunological and virological features of varicella zoster virus (VZV) infection of humans. We have shown earlier that latent SVV infection can be established in African green monkeys by exposing SVV-seronegative monkeys to an SVV infected cage-mate monkey. In this study, we established natural SVV infection in 7 cynomologous monkeys. Six \ developed varicella rash within two weeks post exposure. SVV DNA was detected in multiple ganglia but not in lung or liver in 2 of 7 monkeys within 3 months, and SVV RNA was not detected in these ganglia. Six months post infection, we treated four of the remaining 5 monkeys with a single dose (200 cGy) of X-irradiation followed by the immunosuppressive drugs, tacrolimus (80-300 mg/kg/day) and prednisone (1 mg/kg/day) for 4 months. Varicella-like rash was observed in one of the immunosuppressed monkey and in the control monkey at 5 weeks post-immunosuppression. The monkeys were sacrificed at monthly intervals following immunosuppression and ganglionic and non ganglionic tissues were analyzed for the presence of SVV DNA and RNA. SVV DNA was detected in at least in one ganglion from each of the 5 immunosuppressed animals and in lung or liver from 2 of 4 immunosuppressed animals, and in lung and liver from the control animal. RNA specific for SVV ORF 63 was detected in 2 of 4 immunosuppressed monkey and in the control monkey. RNA specific for SVV ORFs 9 or 28 were detected in ganglia from 2/4 immunosuppressed monkeys but not in the control monkey. Our results show that latent SVV infection can be established in cynomologous monkeys and that SVV reactivation can occur, independent of immunosuppression.