PATHOGENESIS OF MEASLES VIRUS INFECTIONS

麻疹仍然是一个主要的世界卫生问题，但这种疾病的发病机制 疾病一直很难研究，人们对它的了解也不完全。这个 感染导致免疫抑制，部分原因可能是复制 在免疫系统的细胞内。麻疹也与某些 神经系统并发症，与缺乏(包涵体)有关 脑炎)或不适当的(感染后脑脊髓炎)免疫 对病毒复制缺陷的反应(亚急性硬化症 全脑炎)。这些疾病的发病率与年龄相关 并发症表明，宿主在感染时的成熟状态 感染很重要。小鼠麻疹病毒感染模型的建立 中枢神经系统已经发育，新生的小鼠在其中发育 断奶小鼠发生生产性病毒感染的急性脑炎 非生产性病毒引起的非炎症性脑病 感染。在断奶小鼠体内，病毒抗原是合成的，但 核衣壳没有组装。此模型提供了一个更改的示例 由于宿主细胞成熟而导致的病毒表达，并提供了机会 成熟神经系统对麻疹病毒作用的研究 复制。使用最近开发的DNA序列克隆 与麻疹RNA互补，并结合原位检测新技术 杂交和同步免疫细胞化学，我们建议研究 这一模型以及来自自然麻疹病毒患者的样本 感染，有以下具体目标：(1)确定是否 麻疹病毒在小鼠脑内复制的年龄依赖性限制 发生在基因组长度的RNA的复制水平上，通过使用单独的 正、负义RNA的探针。(2)确定 特定亚类白细胞对肺炎衣原体感染的易感性 麻疹病毒在实验性小鼠和自然人类感染中的作用 用单抗免疫过氧化物酶鉴定细胞类型 组织化学原位同时检测麻疹RNA 杂交。(3)确定麻疹的细胞和器官分布 有脑炎和无脑炎的致命人类病例中的病毒，通过使用 免疫细胞化学和原位杂交同步进行。 这项工作的意义在于它有助于理解 麻疹病毒感染及其对免疫系统和中枢神经系统的影响 神经系统，并潜在地理解 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.