PATHOGENESIS OF MEASLES VIRUS INFECTIONS

麻疹仍然是一个主要的世界卫生问题，但其发病机制 这种疾病很难研究，也不完全了解。 的 感染导致免疫抑制，可能部分是由于复制 在免疫系统的细胞内。 麻疹也与某些 神经系统并发症，与缺陷（包涵体 脑炎）或不适当（感染后脑脊髓炎）免疫 反应，或有缺陷的病毒复制（亚急性硬化 全脑炎）。 这些疾病发生率的差异 并发症表明，宿主的成熟状态，在时间的 感染很重要。 麻疹病毒感染小鼠模型的建立 中枢神经系统已经发育， 断奶小鼠急性脑炎合并病毒感染 患上非炎性脑病， 感染 在断奶小鼠中，病毒抗原被合成，但 核衣壳不组装。 这个模型提供了一个例子， 由于宿主细胞成熟而导致病毒表达， 研究成熟的神经系统对麻疹病毒的影响 复制的 使用最近开发的DNA序列克隆 与麻疹RNA互补，再加上新的原位技术， 杂交和同时免疫细胞化学，我们建议研究 该模型以及来自天然麻疹病毒患者的标本 感染，具有以下具体目标：（1）确定是否 麻疹病毒在小鼠脑中复制的年龄依赖性限制 发生在基因组长度的RNA复制水平，通过使用单独的 用于正和负义RNA的探针。 (2)确定 白细胞的特定亚类对感染的易感性 麻疹病毒在实验鼠和自然人感染， 用单克隆抗体免疫过氧化物酶鉴定细胞类型 组织化学和原位同步检测麻疹RNA 杂交方法 (3)确定麻疹的细胞和器官分布 病毒在致命的人类病例与脑炎，通过使用 同时进行免疫细胞化学和原位杂交。 这项工作的意义在于它对理解 麻疹病毒感染及其如何影响免疫系统和中枢神经系统 神经系统，并有可能了解的基本原则， 宿主细胞成熟阶段对病毒复制的影响。

Measles remains a major world health problem, but the pathogenesis of this disease has been difficult to study and is incompletely understood. The infection causes immune suppression, probably due in part to replication within cells of the immune system. Measles is also associated with certain neurological complications, related to deficient (inclusion body encephalitis) or inappropriate (postinfectious encephalomyelitis) immune responses, or to defective viral replication (subacute sclerosing panencephalitis). Age-related differences in the incidence of these complications suggest that the maturation state of the host at the time of infection is important. A murine model of measles virus infection of the central nervous system has been developed in which newborn mice develop acute encephalitis with a productive virus infection while weanling mice develop a non-inflammatory encephalopathy with a non-productive virus infection. In the weanling mouse viral antigens are synthesized, but nucleocapsids are not assembled. This model provides an example of altered virus expression due to host cell maturation and offers the opportunity to study the effects of a maturing nervous system on measles virus replication. Using recently developed clones of DNA sequences complementary to measles RNA, coupled with new techniques of in situ hybridization and simultaneous immunocytochemistry, we propose to study this model, as well as specimens from patients with natural measles virus infection, with the following specific aims: (1) To determine if the age-dependent restriction of measles virus replication in the mouse brain occurs at the level of replication of genomic-length RNA, by using separate probes for positive and negative sense RNA. (2) To determine the susceptibility of specific subclasses of leukocytes to infection with measles virus in both experimental murine and natural human infections by identifying the cell type with use of monoclonal antibody immunoperoxidase histochemistry and simultaneously detecting measles RNA by in situ hybridization. (3) To determine the cell and organ distribution of measles virus in fatal human cases with and without encephalitis, by using simultaneous immunocytochemistry and in situ hybridization. The significance of this work lies in its contribution to the understanding of measles virus infection and how it affects the immune system and central nervous system, and potentially to understanding fundamental principles of the influence of host cell maturation stage on viral replication.