Functional analysis of the novel upstream ORF in enteroviruses

肠病毒属由一大群病毒组成，其中已知有100多种血清型是人类病原体。人类的疾病表型范围从亚临床到急性弛缓性麻痹、心肌炎和脑膜炎。直到最近，人们还认为肠病毒在一个长长的开放阅读框中编码所有的蛋白质。然而，现在已知，在许多肠病毒中，一个小的上游开放阅读框（uORF）编码一种称为UP（上游蛋白）的附加蛋白。uORF被翻译的机制是未知的，因此UP表达的调控是不确定的。这项工作的目的是解决这些问题，使用报告系统和核糖体分析，除其他技术。在先前发表的工作的基础上，我们研究了echovirus 7内部核糖体进入位点的结构域VI茎环结构与uORF翻译之间的关系。通过分析echovirus 7感染细胞的起始核糖体，我们描述了病毒感染过程中起始事件的特征。我们的发现为肠病毒感染细胞的基因表达机制提供了机制上的见解。

The genus Enterovirus consists of a large group of viruses, of which over 100 serotypes are known to be human pathogens. Disease phenotype in humans ranges from sub-clinical to acute flaccid paralysis, myocarditis, and meningitis. Until recently, it was thought that enteroviruses encode all their proteins in a single long open reading frame. However, it is now known that in many enteroviruses a small upstream open reading frame (uORF) encodes an additional protein termed UP (Upstream Protein). The mechanism by which the uORF is translated is unknown and thus the regulation of UP expression is undetermined. This work aims to address these questions using reporter systems and ribosome profiling, amongst other techniques. Building on previously published work, we investigate the relationship between the structure of the domain VI stem loop of the echovirus 7 internal ribosome entry site and translation of the uORF. Through profiling initiating ribosomes of echovirus 7 infected cells, we characterise the profile of initiation events during virus infection. Our findings provide mechanistic insights into gene expression mechanism of enterovirus-infected cells.