TROPISM OF HERPESVIRUS FOR THE OLFACTORY SYSTEM

虽然成年人的脑炎可以由几种病毒引起， 单纯疱疹病毒1型（HSV-1）是一种传染性病原体， 被认为是导致美国人散发性致命性脑炎的主要原因。 美国的 在人类中，HSV-1脑炎通常是 以颞叶坏死性炎性病变为特征 但有趣的是，最近的研究表明，HSV-1可以 也会引起严重的行为或记忆障碍， 没有明显的脑部感染迹象 最近的研究表明， HSV-1能够在人脑中建立潜伏期， 从动物模型中证实的结果表明， 通过嗅觉途径的入侵可能是 产生与急性脑炎相关的立体型脑炎病变 或者是这种疾病的重新激活形式 证据已经获得 从几个动物模型中发现了一种 糖蛋白作为癫痫发作的原因，并在HSV-1的能力 扩散到中枢神经系统（CNS）中心 嗅觉、记忆和学习，包括嗅觉， 球、皮质、内嗅皮质、杏仁核和海马体。 在这项建议中，非常特殊类型的胞内重组 病毒将被用作工具来检查这个领域。 糖蛋白，因为它们与HSV-1传播到 特定的CNS感觉中枢，诱导边缘癫痫发作，以及 导致学习障碍。 将对实验感染动物进行评估， 产生感染的临床体征，包括癫痫发作 发展，对于脑炎的脑电图证据， 以及CNS内病毒特异性产物的出现 嗅觉系统和中枢神经系统的感觉区参与 组织病理学和病毒学的记忆和学习 技术. 为了将CNS区域的感染与 学习，动物将被测试他们学习一个复杂的能力， 鼻内感染后的异中心空间任务。 这些研究 这是我们理解病毒因素的基础， 导致菌株引起的CNS疾病表现 以及开发安全有效的HSV 疫苗。

Although encephalitis of human adults can be caused by several infectious agents, herpes simplex virus type 1 (HSV-1) is considered a leading cause of sporadic fatal encephalitis in the United States. In humans, HSV-1 encephalitis is often characterized by necrotizing inflammatory lesions in the temporal lobes, but interestingly, recent studies indicate that HSV-1 can also induce severe behavioral or memory disturbances in the absence of overt signs of brain infection. recent studies showing that HSV-1 can establish latency within the human brain have validated findings from animal models that suggested viral invasion via the olfactory pathway may be fundamental to producing the sterotypic encephalitic lesions associated with acute or reactivated forms of this disease. Evidence has been obtained from several animal models that implicates a specific viral glycoprotein as a cause of seizures, and I n the ability of HSV-1 to spread to the central nervous system (CNS) centers involved with olfaction and memory and learning, including the olfactory bulb, cortex, the entorhinal cortex, amygdala, and hippocampus. In this proposal, very specific types of intratypic recombinant viruses will be utilized as tools to examine th3e domains of this glycoprotein as they relate to the ability of HSV-1 to spread to specific CNS sensory centers, to induce limbic seizures, and to induce learning disabilities after intranasal infection. Experimentally infected animals will be assessed for the production of clinical signs of infection including seizure development, for electroencephalographic evidence of encephalitis, and for the appearance of viral-specific products within the CNS olfactory system and the sensory areas of the CNS involved with memory and learning by histopathological and virological techniques. To correlate infection of CNS areas involved in learning, animals will be tested for their ability to learn a complex allocentric-spatial task after intranasal infection. these studies are fundamental to our understanding of the viral factors that contribute to the manifestations of CNS disease seen with strains of HSV and to the development of safe and effective HSV vaccines.