SIMIAN VARICELLA VIRUS INFECTION AND LATENCY IN THE NONHUMAN PRIMATE

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得主要资金，因此可以在其他CRISP条目中表示。所列机构为中心，不一定是研究者所在机构。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。在这项研究中，我们建立了自然SVV感染7食蟹猴。 6例在暴露后2周内出现水痘皮疹。 3个月内，7只猴中有2只在多个神经节中检测到SVV DNA，但在肺或肝中未检测到SVV RNA。 感染后6个月，我们用单剂量（200 cGy）X射线照射治疗其余5只猴中的4只，然后用免疫抑制药物他克莫司（80-300 mg/kg/天）和泼尼松（1 mg/kg/天）治疗4个月。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。在免疫抑制后每月处死猴，分析神经节和非神经节组织中SVV DNA和RNA的存在。在5只免疫抑制动物中的每只动物的至少一个神经节中、4只免疫抑制动物中的2只动物的肺或肝中以及对照动物的肺和肝中检测到SVV DNA。在4只免疫抑制猴中的2只和对照猴中检测到SVV ORF 63特异性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，潜在的SVV感染可以建立在食蟹猴和SVV再激活可以发生，独立的免疫抑制。

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.