SIMIAN VARICELLA VIRUS INFECTION AND LATENCY IN THE NONHUMAN PRIMATE

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 灵长类动物感染水痘病毒(SVV)具有人类水痘带状疱疹病毒(VZV)感染的临床、病理、免疫学和病毒学特征。我们早些时候已经证明，通过将SVV血清阴性的猴子暴露于感染SVV的笼友猴子，可以在非洲绿猴中建立潜伏的SVV感染。对自然感染和潜伏感染猴水痘病毒(SVV)的食蟹猴进行了一系列的辐射和免疫抑制药物治疗研究，以揭示病毒反应的触发因素。第一项研究表明，单次剂量(200cGyX射线)照射后，他克莫司(80-300 mg/kg/天)和泼尼松(1 mg/kg/天)治疗4个月的动物表现出重新激活。免疫抑制后5周，1只免疫抑制猴和1只对照猴出现水痘样皮疹。4/4的动物至少有1个神经节和2/4的动物的肺或肝脏中检测到SVV DNA，而对照组动物的肺和肝脏中均为阳性。在2/4免疫抑制猴和对照猴中均检测到SVV ORF 63RNA。在2/4免疫抑制猴的神经节中检测到针对SVV ORF9或28的特异性RNA，而在对照猴中未检测到。我们的结果表明，食蟹猴体内可以建立潜伏的SVV感染，并发生实验性的病毒再激活。对9只食蟹猴的第二项研究已经启动，以测试其中一种实验试剂他克莫司，作为重新激活潜伏的SVV感染的触发器，这也是在食蟹猴身上，目前正在进行中。

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.