SIMIAN VARICELLA--VZV PATHOGENESIS & LATENCY

描述(摘自申请者摘要)：水痘带状疱疹病毒 (VZV)引起水痘(水痘)和带状疱疹(带状疱疹)，疾病 与儿童和老年人的严重发病率有关， 分别是严重和危及生命的感染 免疫功能受损的个体。不幸的是，我们对VZV的理解 由于缺乏令人满意的动物，致病机制和潜伏期有限 模特们。猴水痘病毒(SVV)在非人类灵长类动物中引起自然的 在临床和病原学上类似于人类VZV感染的疾病。 根据VZV和SVV的抗原性和遗传相关性以及 人与猿猴水痘、非人SVV感染的相似性 灵长类动物为人类VZV感染提供了一个有用的动物模型。 P.I.已经表征了SVV的分子特性，并开发了一种 特定的SVV探针和试剂的数量。这个项目的总体目标是 建议利用猿猴水痘模型研究水痘 水痘发病机制和潜伏期的分子基础。具体目标 包括： 1)表达SVV糖蛋白E(GE)、gB和即刻早期基因62 (IE62)基因在重组表达载体中的表达并产生单特异性 表达蛋白的抗血清。该抗血清将被用来检测 受感染猴子神经节和其他组织中的SVV抗原。2)做得更好 用SVV检测确定水痘潜伏期 鼻咽感染和病毒血症。3)调查儿童的SVV感染情况 感染原发性水痘期间的感觉神经节等组织 猴子。4)检测SVV基因表达并确定细胞位置 潜伏感染的感觉神经节中的病毒DNA和/或RNA 猴子。5)生成基于COSMID的SVV重组系统 构建SVV胸苷酶、尿嘧啶糖基酶和糖蛋白C(GC) 突变体，将在未来的研究中使用，以研究 SVV特异性基因在病毒致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.