MOLECULAR MECHANISMS OF CORONAVIRUS NEUROPATHOGENICITY

这个项目的总体目标是理解分子 MHV神经发病机制的研究。这个项目的主要目标是 了解病毒组织和细胞嗜性的分子基础。 在上一个赠款期间取得的进展确定了几个 MHV感染的细胞受体。然而，这些受体不能 完全解释了病毒的组织嗜性。在此授权期内，我们 建议鉴定和研究MHV和MHV的更多细胞受体 病毒进入的过程。将执行三个具体项目： (1)脑特异性MHV受体的特性。我们已经确定了 一种仅在大脑中表达的癌胚抗原(CEA)， 到目前为止，唯一发现的这类CEA分子。我们将决定 它作为MHV受体的功能，它的神经生物学和在 大脑的发育。它的生化特性和时间和 我们还将研究大脑中的空间表达模式。(2) 在小鼠中鉴定MHV的额外脑特异性受体 老鼠和人类。我们的数据表明，不止一个CEA分子可以 也可作为MHV受体。我们想要检查CEA分子 在其他物种和其他CEA分子中，小鼠可以作为MHV 感受器。这些研究将揭示MHV的潜在机制。 在老鼠以及大鼠和灵长类动物中的感染。(3)识别 与MHV受体相互作用的细胞蛋白及MHV结构 蛋白质。我们的研究表明，受体本身并不是 足以让病毒进入细胞。其他细胞因素包括 必填项。初步数据显示，这些细胞因子可能 直接或间接与受体或病毒结构相互作用 蛋白质。因此，我们将使用生化方法和分子 鉴定与其中任何一种相互作用的细胞蛋白的生物学方法 CEA分子或MHV结构蛋白。这些组件的功能 将研究病毒进入过程中的蛋白质。这三个人 项目将使我们能够了解病毒组织的分子基础 向心性。

The overall objective of this project is to understand the molecular mechanism of MHV neuropathogenesis. The major goal of this project is to understand the molecular basis of viral tissue and cellular tropism. The progress made in the previous grant period has identified several cellular receptors for MHV infection. However, these receptors cannot totally account for viral tissue tropism. In this grant period, we propose to identify and study additional cellular receptors for MHV and the process of virus entry. Three specific projects will be performed: (1) Characterization of brain-specific MHV receptors. We have identified a carcinoembryonic antigen (CEA) which is expressed only in the brain, the only CEA molecule of this kind identified so far. We will determine its function as an MHV receptor, its neurobiology and role in the development of brain. Its biochemical properties and temporal and spatial expression patterns in the brain also will be examined. (2) Identification of additional brain-specific receptors for MHV in mice, rats and humans. Our data suggested that more than one CEA molecule can also serve as an MHV receptor. We want to examine whether CEA molecules in other species and other CEA molecules in mice can serve as MHV receptors. These studies will reveal the potential mechanism of MHV infections in mice as well as rats and primates. (3) Identification of cellular proteins interacting with MHV receptors and MHV structural proteins. Our studies have indicated the receptors alone are not sufficient to allow virus to enter cells. Other cellular factors are required. Preliminary data suggested that these cellular factors might interact directly or indirectly with receptors or with viral structural proteins. Therefore, we will use biochemical methods and molecular biology approaches to identify cellular proteins interacting with either CEA molecules or MHV structural proteins. The functions of these proteins in the viral entry process will be studied. These three projects will allow us to understand the molecular basis of viral tissue tropism.