Evolution of Human C-cluster Enteroviruses

描述(申请人提供)：C-簇肠病毒是一组 在Picornav7 DAE中具有高度传染性的肠道病毒属，是 以密切相关的基因类型为特点，但致病机理却截然不同 属性(脊髓灰质炎与呼吸道疾病)。它们可以细分为 分成3个脊髓灰质炎病毒(PV)和11个C群柯萨奇A病毒(C-Cay) 主要不同的是它们对细胞受体(hPVR和ICAM-1， )。这些病毒的集群是基于非常有限的 关于基因分型的知识。C-CAV的原子级结构 病毒粒子是未知的，因此不可能将表面功能与结构联系起来 因此，与病毒粒子/受体相互作用的进化有关。 我们建议分析C-簇肠病毒之间的关系，目的是 在阐明这些病毒选择成为 柯萨奇病毒或脊髓灰质炎病毒。这将包括确定基因类型和 几种C-Cavs的分子生物学、晶体结构的阐明 一株C-Cay病毒粒子及其抗原性的研究 受体/病毒粒子相互作用。 脊髓灰质炎病毒与其人类宿主之间的关系发生了戏剧性的变化 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领先， 矛盾的是，对毁灭性的脊髓灰质炎流行，这反过来又促使 有效疫苗的开发。事实上，目前正在努力 在全球根除脊髓灰质炎病毒。我们已经考虑到一种可能性，即在一个 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类药物可能会转换 受体(ICAM-L到CD155)作为新的脊髓灰质炎病毒进化。来评估这一点 我们建议建立一个模型系统来测试 C-簇肠病毒的物种形成。

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.