HN GLYCOPROTEIN ROLE IN MUMPS VIRUS NEUROVIRULENCE

流行性腮腺炎病毒是一种常见的人类病原体， 神经系统（CNS）。 流行性腮腺炎病毒株的不同在于， 细胞致病性（它们在体外引起的细胞病理学程度） 及其神经毒力（侵入中枢神经系统并感染神经元的能力） 而且在体外和体内 生物效应。 这些应变依赖的分子基础 差异是未知的，并且是所提出的实验的焦点。 初步证据表明， 细胞致病性和神经毒力至少部分来自 病毒HN糖蛋白结构的变化，其介导 病毒体与宿主细胞的结合。 拟议的实验旨在 表征HN糖蛋白的结构并鉴定 有助于腮腺炎病毒致细胞病变性的功能结构域， 神经毒性 具体来说，将采用三种不同的选择方案， 用于分离与亲本腮腺炎病毒不同的腮腺炎病毒变体 病毒株的HN结构只有微小的改变， 糖蛋白 结构变更将在以下级别定义： 腮腺炎病毒变异体的糖蛋白氨基酸序列， 与亲本腮腺炎病毒株在体外和体内生物学上不同， 影响;以这种方式，在初级结构的变化，导致一个 糖蛋白功能和病毒毒力的改变将是 鉴定 最后，将尝试产生多克隆 针对HN糖蛋白的推定功能结构域的抗体， 使用与选择的多肽具有序列同源性的合成肽作为免疫原 完整糖蛋白的区域。 抗肽抗体识别 将测试天然构型的HN糖蛋白的活性 在体外功能测定和新生儿保护作用 流行性腮腺炎脑膜脑炎仓鼠模型。 预计该 这些研究的结果将提供深入了解的结构， HN糖蛋白的功能结构域，并将有助于 了解腮腺炎病毒感染中枢神经系统的发病机制。

Mumps virus is a common human pathogen that frequently invades the central nervous system (CNS). Strains of mumps virus differ in their cytopathogenicity (the degree of cytopathology that they cause in vitro) and their neurovirulence (the ability to invade the CNS and infect neurons) and there appears to be a correlation between the in vitro and in vivo biological effects. The molecular basis for these strain-dependent differences is not known and is the focus of the proposed experiments. Preliminary evidence suggests that the strain-dependent differences in cytopathogenicity and neurovirulence result, at least in part, from variation in the structure of the viral HN glycoprotein which mediates virion binding to host cells. The proposed experiments are designed to characterize the structure of the HN glycoprotein and to identify the functional domains that contribute to mumps virus cytopathogenicity and neurovirulence. Specifically, three different selection protocols will be used to isolate mumps virus variants that differ from the parental mumps virus strain by only minor alterations in the structure of the HN glycoprotein. The structural alterations will be defined at the level of the glycoprotein's amino acid sequence for those mumps virus variants that differ from the parental mumps virus strain in vitro and in vivo biological effects; in this way, the changes in primary structure that result in a modification in glycoprotein function and in virus virulence will be identified. Finally, an attempt will be made to generate polyclonal antibodies against putative functional domains of the HN glycoprotein by using as immunogens synthetic peptides with sequence homology to selected regions of the intact glycoprotein. Anti-peptide antibodies that recognize the HN glycoprotein in its native configuration will be tested for activity in in vitro functional assays and for a protective effect in the newborn hamster model of mumps meningoencephalitis. It is anticipated that the results of these studies will provide insight into the structure of the functional domains of the HN glycoprotein and will contribute to the understanding of the pathogenesis of mumps virus infection of the CNS.