SIMIAN VARICELLA VIRUS INFECTION AND LATENCY IN THE NONHUMAN PRIMATE

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 猴水痘病毒（SVV）感染灵长类动物与人水痘带状疱疹病毒（VZV）感染具有相同的临床、病理、免疫学和病毒学特征。 我们先前已经证明，通过将SVV血清阴性猴暴露于SVV感染的笼友猴，可以在非洲绿色猴中建立潜伏性SVV感染。 提出了一系列研究，测试自然和潜伏感染猴水痘病毒（SVV）的食蟹猴的辐射和免疫抑制药物治疗，以描绘病毒反应的触发因素。第一项研究表明，接受单剂量（200 cGy）X射线照射，然后接受他克莫司（80-300 mg/kg/天）和泼尼松（1 mg/kg/天）治疗4个月的动物显示出重新激活。 免疫抑制后5周，在1只免疫抑制猴和对照猴中观察到静脉曲张样皮疹。 在4/4只动物的至少一个神经节和2/4只动物的肺或肝脏中检测到SVV DNA，而对照动物的肺和肝脏中为阳性。 在2/4免疫抑制猴和对照猴中检测到SVV ORF 63 RNA。在2/4免疫抑制猴的神经节中检测到SVV ORF 9或28的特异性RNA，但在对照猴中未检测到。我们的研究结果表明，潜伏性SVV感染可以建立在食蟹猴和实验的病毒再活化发生。 在9只食蟹猴中开始了第二项研究，以测试一种实验药物他克莫司作为重新激活潜伏性SVV感染的触发剂，也是在食蟹猴中，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.