Evolution of Human C-cluster Enteroviruses

描述（由申请方提供）：C簇肠道病毒是一组 小核糖核酸病毒科肠道病毒属内的高传染性因子， 以基因型密切相关但致病性差异巨大为特征 特性（脊髓灰质炎与呼吸系统疾病）。它们可以细分 3种脊髓灰质炎病毒（PV）和11种C簇科萨基A病毒（C-CAy） 其主要区别在于它们使用细胞受体（hPVR和ICAM-1， 分别）。这些病毒的聚类是基于非常有限的 关于基因型的知识。C-CAV的原子级结构 病毒粒子是未知的，使得不可能将表面功能与结构联系起来 并因此涉及病毒体/受体相互作用的进化。 我们建议分析C簇肠道病毒之间的关系， 阐明这些病毒选择成为 科萨基或脊髓灰质炎病毒。这将包括确定基因型， 几种C-CAV的分子生物学，晶体结构的阐明 一种C-CAy病毒粒子及其抗原特性的研究， 受体/病毒体相互作用。 脊髓灰质炎病毒与其人类宿主之间的关系发生了巨大变化 在二十世纪。首次实行新的卫生措施 上个世纪初工业化国家的时间， 矛盾的是，毁灭性的脊髓灰质炎流行，反过来， 研制有效的疫苗。事实上，正在努力 在全球根除脊髓灰质炎病毒。我们考虑了一种可能性， 世界上没有脊髓灰质炎病毒和抗脊髓灰质炎抗体一些C-CA V可能会转换 受体（ICAM-1至CD 155）进化为新型脊髓灰质炎病毒。为了评估这一点 方案，我们建议建立一个模型系统，以测试的可能性， C簇肠道病毒的物种形成。

DESCRIPTION (provided by applicant): C-Cluster enteroviruses are a group of highly infectious igents within Picornav7 dae, genus Enterovirus, that are characterized by closely related genotypes but vastly different pathogenic properties (poliomyelitis vs. respiratory disease). They can be sub-divided into three poliovirus (PV) and 11 C-cluster coxsackie A virus (C-CAy) species that differ principally in their use of the cellular receptor (hPVR and ICAM-1, respectively). The clustering of these viruses is based on very limited knowledge regarding genotypes. The structure at the atomic level of C-CAV virions is unknown making it impossible to relate surface function to structure and, thus, to the evolution of virion/receptor interaction. We propose to analyze the relationship between C-cluster enteroviruses, aiming at elucidating the evolutionary pathway by which these viruses chose to become coxsackie or polioviruses. This will include the determination of genotypes and molecular biology of several C-CAVs, the elucidation of the crystal structure of a C-CAy virion and its antigenic properties, and the analysis of receptor/virion interaction. The relationship between poliovirus and its human host has dramatically changed during the twentieth century. New measures of hygiene practiced for the first time in industrialized countries at the beginning of last century led, paradoxically, to devastating poliomyelitis epidemics that, in turn, prompted the development of effective vaccines. Indeed, efforts are underway to eradicate poliovirus globally. We have entertained the possibility that in a world free of poliovirus and anti-polio antibodies some C-CA Vs may switch receptors (ICAM-l to CD155) to evolve as novel polioviruses. To assess this scenario we propose to establish a model system to test possibilities of speciation of C-cluster enteroviruses.