BIOLOGY OF C CLUSTER COXSACKIEVIRUSES

在这个新的应用中，维默博士建议检查各种 柯萨奇病毒C簇（C-CAV）中的不同小核糖核酸病毒， 是基于序列相似性定义的组， 含有脊髓灰质炎病毒和各种柯萨奇病毒，包括CAV 21和CAV 24。 该提案的总体目标是获得更多关于这些问题的信息， 病毒，并从其中一些开发新的模型系统。在这些 他们将利用他们对脊髓灰质炎病毒的广泛知识和研究 系统作为一个模型，建议为病毒开发系统， 在这里学习。人们提出了各种不同的实验， 几种不同的病毒将在拟议的不同部分进行检查， 问题研究在研究过程中，研究人员将 在病毒中进行选择，以确定要研究的病毒 更详细地描述。 有四个具体目标。首先是进行一些非常基本的病毒学研究 对C-CAV的研究--但主要是对CAV 21的研究--以确定它们中的哪一种可以增长 组织培养，并研究其生长特性及其它 病毒粒子的一般性质。其他研究将是抗原性的 病毒粒子的性质，包括病毒粒子的制备和定位， 病毒的中和表位。第二个具体目标是确定 C-CAV的基因组特性，包括全长 几种病毒的克隆和感染性cDNA，特别是 科萨基A24病毒（CAV 24）和CAV 24 v，后者是引起 出血性结膜炎这些序列也将用于研究 各种C-CAV之间的进化关系。其他研究将 包括CAV 21的无细胞从头合成，以及各种研究， 重组不同C-CAV之间的基因组片段，以绘制它们的 生物差异。第三个具体目标是结晶的衣壳 一种或多种病毒，然后确定病毒体的结构， 通过X射线晶体学，在与Michael Rossmann和 普渡大学的理查德·库恩。第四个具体目标是确定 这些病毒的衣壳和受体之间的相互作用，包括 ICAM-1、ICAM-1、ICAM-1与CAV 21 a的关系以及CAV 24与CAV 24 v的关系。

In this new application Dr. Wimmer proposes to examine a variety of different picornaviruses in the C cluster of coxsackievirus (C-CAV), which is the group that are defined on the basis of sequence similarities as containing poliovirus, and various coxsackieviruses, including CAV21 and CAV24. The overall objective of the proposal is to gain more information about those viruses, and also to develop new model systems from some of them. In these studies they will use their extensive knowledge and studies of poliovirus systems as a model for proposing the systems to be developed for the viruses to be studied here. There are a variety of different experiments proposed, and several different viruses will be examined in various parts of the proposed studies. During the course of the studies the investigators will make selections among the viruses in order to decide on the virus (es) to be studied in more detail. There are 4 specific aims. The first is to perform some very basic virological studies of the C-CAVs--but mainly on CAV21--to determine which of them can grow well in tissue culture, and then to study the growth characteristics and other general properties of the virion. Other studies will be of the antigenic properties of the virion, including the preparation and mapping of the neutralizing epitopes of the virus. The second specific aim is to define the genomic properties of the C-CAVs, including the preparation of full-length clones and infectious cDNAs of several of the viruses, in particular the Coxsackie A24 virus (CAV24), and the CAV24v that is a variant the causes hemorrhagic conjunctivitis. The sequences will also be used in studies of the evolutionary relationships between the various C-CAVs. Other studies would include the cell free de novo synthesis of CAV21, and various studies involving recombining genomic segments among the different C-CAVs in order to map their biological differences. The 3rd specific aim is to crystallize the capsid of one or more of those viruses, and then determine the structures of the virion by X-ray crystallography, in collaborative studies with Michael Rossmann and Richard Kuhn at Purdue University. The 4th specific goal is to define the interactions between the capsid and the receptors of those viruses, including ICAM-1 and DAF with CAV21a, and the relationships between CAV24 and CAV24v.