SIMIAN VARICELLA MODEL FOR HUMAN VZV INFECTIONS

水痘-带状疱疹病毒(VZV)是水痘的病原体 水痘和带状疱疹(带状疱疹)。而VZV感染是 通常是良性的，可能是严重的，并危及生命 免疫功能受损的人，特别是癌症患者， 移植受者和艾滋病患者。不幸的是，研究 VZV感染的发病机制及抗病毒治疗的研究进展 受阻，因为VZV在实验中不会导致疾病 动物。然而，猿猴水痘是由猿猴引起的 水痘病毒(SVV)在临床和病理上与 人类水痘，已被证明是一个很好的动物模型 用于人类VZV感染。这项研究的总体目标 方案是利用猿猴水痘模型作为研究手段 人VZV感染的致病机制及其研制与检测 潜在的VZV亚单位疫苗和其他抗病毒疗法。 而VZV和SVV已被证明具有抗原性和 从基因上讲，人们对这种分子知之甚少 属性或SVV。因此，这一行动的前四个具体目标 建议是1)确定SVV基因组的结构，2) 识别SVV和DNA之间的同源区域，3)表征 SVV糖蛋白，以及4)识别交叉反应的VZV和SVV 糖蛋白。这些信息将提供一个分子基础 为进一步研究猿猴的发病机制奠定了基础 水痘。特定的目标#5将决定对 SVV感染猴体内的单个SVV糖蛋白和Will 研究这些糖蛋白在诱导免疫中的作用 到猿猴水痘。VZV免疫已被证明 以保护猴子免受随后的SVV挑战。 特定目标#6将决定对VZV的免疫反应 可能在诱导这种免疫力中起重要作用的糖蛋白。

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.