TROPISM OF HERPESVIRUS FOR THE OLFACTORY SYSTEM

尽管成人脑炎可由多种原因引起 感染因子，单纯疱疹病毒1型(HSV-1)是 被认为是散发性致死性脑炎的主要原因 美国。在人类中，HSV-1脑炎通常是 以颞部坏死性炎症性病变为特征 但有趣的是，最近的研究表明HSV-1可以 也会导致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可以在人脑内建立潜伏期 动物模型的验证结果表明，病毒 通过嗅觉通路的侵袭可能是 产生与急性脑炎相关的体型脑炎损害 或重新激活这种疾病的形式。已经获得了证据 从几个涉及特定病毒的动物模型中 糖蛋白是癫痫发作的原因，与HSV-1的能力有关 扩散到涉及的中枢神经系统(CNS)中心 嗅觉、记忆和学习，包括嗅觉 鳞茎、皮质、内嗅皮质、杏仁核和海马体。 在这项提议中，非常特定类型的非典型重组 病毒将被用作工具来检查这三个域 糖蛋白与HSV-1传播到 特定的中枢感觉中心，诱导边缘癫痫发作，并 鼻腔感染后诱发学习障碍。 实验感染的动物将被评估为 产生感染的临床症状，包括癫痫 发展，脑炎的脑电证据， 以及在中枢神经系统内出现病毒特异性产品 嗅觉系统和中枢神经系统的感觉区域 组织病理学和病毒学研究中的记忆和学习 技巧。与中枢神经系统感染的相关性研究 学习，动物将被测试它们学习复合体的能力 鼻腔感染后的异地着丝点-空间作业。这些研究是 这是我们理解病毒因素的基础 导致中枢神经系统疾病的表现与菌株有关 为HSV的发展和安全有效的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.