SIMIAN VARICELLAMODEL FOR HUMAN VZV INFECTIONS

水痘-带状疱疹病毒（Varicella-zostervirus，VZV）是水痘的病原体 水痘和带状疱疹。 虽然VZV感染是 它们通常是良性的，但在某些情况下可能是严重的并危及生命。 免疫功能低下的个体，特别是癌症患者， 移植受者和艾滋病患者。 不幸的是， 关于VZV感染的发病机制和抗病毒治疗的研究 因为VZV在实验中不会引起疾病， 动物 然而，猿猴水痘，这是由猿猴引起的 水痘病毒（SVV），临床和致病性类似 并已被证明是一个很好的动物模型 用于人类VZV感染。 本研究的总体目标是 计划是使用猿水痘模型作为研究手段， 人类VZV感染的发病机制，并开发和测试 潜在的VZV亚单位疫苗和其他抗病毒疗法。 虽然VZV 和sVV已被证明是抗原性的， 基因相关，但对分子水平知之甚少。 属性或SVV。 因此，这四个具体目标 建议是1）确定SVV基因组的结构，2） 鉴定sVV和DNA之间同源性区域，3）表征 sVV糖蛋白，和4）鉴定交叉反应VZV和SVV 糖蛋白这些信息将提供分子基础 为进一步研究猿猴的发病机制奠定了基础 水痘 具体目标#5将决定免疫反应， 在SVV感染的猴中的单个SVV糖蛋白， 研究这些糖蛋白在诱导免疫中的作用 猿猴水痘 VZV免疫已被证明 以保护猴免受随后的sVV攻击。 具体目标#6将决定对VZV的免疫应答 这些糖蛋白可能在引发这种免疫中起重要作用。

Varicella-zoster virus (VZV) is the etiologic agent of varicella (chickenpox) and zoster (shingles). While VZV infections are usually benign, they may be severe and life-threatening in immunocompromised individuals, especially cancer patients, transplant recipients, and AIDS patients. Unfortunately, studies on the pathogenesis of and antiviral therapy for VZV infections are hampered because VZV does not cause disease in experimental animals. However, simian varicella, which is caused by simian varicella virus (SVV), clinically and pathogenically resembles human varicella and has been shown to be an excellent animal model for human VZV infections. The overall goal of this research program is to use the simian varicella model as a means to study the pathogenesis of human VZV infections and to develop and test potential VZV subunit vaccines and other antiviral therapies. While VZV and sVV have been shown to be antigenically and genetically related, very little is known about the molecular properties or SVV. Therefore, the first 4 specific aims of this proposal are to 1) determine the structure of the SVV genome, 2) identify regions of homology between sVV and DNAs, 3) characterize the sVV glycoproteins, and 4) identify cross-reacting VZV and SVV glycoproteins. This information will provide a molecular foundation on which to base further studies on the pathogenesis of simian varicella. Specific aim #5 will determine the immune response to individual SVV glycoproteins in SVV infected monkeys and will investigate the role of these glycoproteins in inducing immunity to simian varicella. Immunization with VZV has been demonstrated to protect monkeys against subsequent challenge with sVV. Specific aim #6 will determine the immune response to the VZV glycoproteins that may be important in eliciting this immunity.