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. A series of studies testing irradiation and immunosuppressive drug treatments of cynomolgus macaques naturally and latently infected with simian varicella virus (SVV) to delineate the triggers of viral reaction are proposed. The first study showed that animals treated with a single dose (200 cGy) of X-irradiation followed by tacrolimus (80-300 mg/kg/day) and prednisone (1 mg/kg/day) for 4 months showed reactivation. Varicella-like rash was observed in one of the immunosuppressed monkey and in the control monkey at 5 weeks post-immunosuppression. SVV DNA was detected in at least in one ganglion from 4/4 animals and lung or liver from 2/4 animals, whereas the control animal was positive in lung and liver. SVV ORF 63 RNA was detected in 2/4 immunosuppressed monkeys 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 cynomolgus macaques and experimental reactivation of virus occur. A second study in nine cynomolgus macaques has been initiated to test one of the experimental agents, tacrolimus, as a trigger to reactivate latent SVV infection, also in cynomolgus macaques, and is currently in progress.