SIMIAN VARICELLA--VZV PATHOGENESIS & LATENCY

描述（改编自申请人的摘要）：水痘带状疱疹病毒 (VZV)引起水痘和带状疱疹， 与儿童和老年人的显著发病率相关， 严重和危及生命的感染， 免疫力低下的人。 不幸的是，我们对VZV的理解 由于缺乏令人满意的动物模型， 模型 猴水痘病毒（SVV）在非人灵长类动物中引起一种天然的 在临床和病理学上类似于人类VZV感染的疾病。 基于VZV和SVV的抗原性和遗传相关性， 人类和猿猴水痘的相似性，非人类的SVV感染 灵长类动物为人类VZV感染提供了有用的动物模型。 私家侦探已经表征了SVV的分子特性，并开发了一种 特定SVV探针和试剂的数量。 这个项目的总体目标是 建议利用猴水痘模型来研究 水痘发病机制和潜伏期的分子基础。 具体目标 为： 1)表达SVV糖蛋白E（gE）、gB和立即早期基因62 （IE62）基因的重组表达载体中，并产生单特异性 表达蛋白的抗血清。 该抗血清将用于检测 感染猴神经节和其他组织中的SVV抗原。 2)更好地 通过SVV检查确定水痘潜伏期 鼻咽感染和病毒血症。 3)为了解SVV感染情况， 感觉神经节和其他组织在感染的原发性水痘期间 猴子 4)检测SVV基因表达并鉴定细胞位点 潜伏感染的感觉神经节中病毒DNA和/或RNA的含量 猴子 5)为了构建SVV的粘粒重组系统， 构建SVV胸苷激酶、尿嘧啶糖基化酶和糖蛋白C（gC） 突变体，将用于未来的研究，以调查的作用， 特异性SVV基因在病毒发病机制和潜伏期中的作用。

DESCRIPTION (Adapted from Applicant's Abstract): Varicella zoster virus (VZV) causes varicella (chickenpox) and zoster (shingles), diseases associated with significant morbidity in children and the elderly, respectively, and severe and life_threatening infections in immunocompromised individuals. Unfortunately, our understanding of VZV pathogenesis and latency is limited due to the lack of satisfactory animal models. Simian varicella virus (SVV) causes in nonhuman primates a natural disease which clinically and pathogenically resembles human VZV infections. Based upon the antigenic and genetic relatedness of VZV and SVV and the similarities of human and simian varicella, SVV infection of nonhuman primates offers a useful animal model for human VZV infections. The P.I. has characterized the molecular properties of SVV and developed a number of specific SVV probes and reagents. The overall goal of this proposal is to utilize the simian varicella model to investigate the molecular basis of varicella pathogenesis and latency. The specific aims are: 1) To express the SVV glycoprotein E (gE), gB, and immediate early gene 62 (IE62) genes in recombinant expression vectors and to generate monospecific antisera to the expressed proteins. This antisera will be used to detect SVV antigens in ganglia and other tissues of infected monkeys. 2) To better define the incubation period of varicella by examination of SVV nasopharyngeal infection and viremia. 3) To investigate SVV infection of sensory ganglia and other tissues during primary varicella in infected monkeys. 4) To examine SVV gene expression and identify the cellular site of viral DNA and\or RNA in sensory ganglia derived from latently infected monkeys. 5) To generate a cosmid_based recombination system for SVV and to construct SVV thymidine kinase, uracil glycosylase, and glycoprotein C (gC) mutants which will be used in a future study to investigate the role of specific SVV genes in viral pathogenesis and latency.