LOCALIZED ANTIBODY SYNTHESIS DURING HSV-1 ENCEPHALITIS

单纯疱疹病毒1型(HSV-1)侵入大脑会产生 伴严重死亡的成人坏死性脑炎 和发病率。急性疾病通常会导致细胞和 脑脊液的蛋白质含量，这在一定程度上反映了一种 中枢神经系统(CNS)内的局部免疫反应。这个 局部病毒特异性抗体产生的正常进化及其 在单纯疱疹病毒性脑炎发病机制中的作用 对这种毁灭性疾病的影响仍然知之甚少。为此， 将进行实验，以详细定义抗体的模式 病毒复制活跃期间脑脊液中的变化 清除，并从急性疾病中恢复。第一，时代性 脑脊液中免疫球蛋白Ig M、Ig G和Ig A的发展 用兔HSE模型进行评估。结果将与 在匹配的血清样本中发现的免疫球蛋白水平。第二，匹配的脑脊液 以及在疾病的不同阶段从感染的兔子身上获得的血清 将检查和比较免疫球蛋白的合成模式 单个病毒诱导的蛋白质和糖蛋白。第三，经济全球化的格局 两种药物对脑炎兔脑脊液中抗体的影响 阿糖腺苷(Ara-A)或阿昔洛韦(阿昔洛韦；阿昔洛韦) 评估以一定精度定义抗病毒药物的潜在作用 HSE过程中局部抗体合成的研究。第四，相同的数量 抗体研究将使用急性和恢复期脑脊液和 从经活检证实的HSE患者身上提取的血清。使用的技术 在这些研究中，包括酶联免疫吸附分析， SDS-聚丙烯酰胺平板凝胶电泳法、免疫沉淀法和 电印迹(Western印迹)程序和各种病毒学分析。 从拟议项目中获得的信息将提供更好的 对中枢神经系统组织内局部免疫反应的认识 HSE的进展，并可能导致改善的发展 控制这种毁灭性疾病的诊断和治疗方法 人类患上脑炎疾病。

Invasion of the brain by herpes simplex virus type 1 (HSV-1) produces a necrotizing encephalitis in adults which is acconpanied by severe mortality and morbidity. Acute disease often leads to changes in the cellular and protein content of the cerebrospinal fluid (CSF) which in part reflect a localized immune response within the central nervous system (CNS). The normal evolution of localized virus-specific antibody production and its role in the pathogenesis of herpes simplex encephalitis (HSE) it recovery from this devastating disease remains poorly understood. To this end, experiments will be performed to define in detail the pattern of antibody changes within CSF during periods of active virus replication, virus clearance, and recovery from acute disease. First, the temporal development of immunoglobulins IgM, IgG, and IgA within CSF will lbe assessed using the rabbit model of HSE. Results will be compared with immunoglobulin levels found in matched serum samples. Second, matched CSF and serum obtained from infected rabbits at various stages of the disease will be examined and compared for the pattern of IgG synthesis to individual virus-induced proteins and glycoproteins. Third, the pattern of antibody changes within the CSF of encephalitic rabbit administered either adenine arabinoside (Ara-A) or acycloguanosine (acyclovir; ACV) will be assessed to define with some precision the potential effect of antivirals on localized antibody synthesis during HSE. Fourth, identical quantitative antibody studies will be performed using acute and convalescent CSF and serum recovered from patients with biopsy-proven HSE. Techniques used during these studies include enzyme-linked immunosorbent assays, SDS-polyactrylamide slab gel electrophoresis, immunoprecipitation and electroblot (Western blot) procedures, and various virological assays. Information derived from the proposed project will provide a better understanding of the localized immune responses within CNS tissue during the progression of HSE and may lead to the development of improved diagnostic and therapeutic approaches for the control of this devastating encephalitis illness in man.