Modeling the contribution of coronavirus cellular tropism to viral pathogenesis

总结 病毒的细胞和组织嗜性被定义为病毒感染的能力 特定的细胞和组织，并由病毒和细胞因素决定。一个 启动感染的重要因素是细胞进入，这取决于感染的能力。 让病毒与其认知受体对接对物种的了解越来越多 ACE 2结构的差异，也许更重要的是组织特异性模式的差异， 的表达强调了使用小鼠模型进行 冠状病毒如SARS-CoV-2致病机理研究 ACE 2用于细胞进入。我们建议实施一项战略， 小鼠模型，其中人ACE 2表达限于单个或多个 气道上皮细胞群。使用这些行，我们将检查 呼吸道中ACE 2表达的细胞模式对事件顺序的影响 在接触SARS-CoV 2冠状病毒之后。

Summary The cell and tissue tropism of viruses is defined as the capacity of a virus to infect specific cells and tissues and is determined by both viral and cellular factors. An important factor for initiation of infection is cell entry, which is dependent on the ability of the virus to dock with its cognitive receptor. A growing understanding of species differences in ACE2 structure and, perhaps more importantly, in tissue specific patterns of expression has underscored the potential limitations in the use of mouse models for the study of disease pathogenesis of coronaviruses such as SARS-CoV-2 that rely on ACE2 for cellular entry. We propose to implement a strategy for the rapid generation of mouse models in which human ACE2 expression is limited to individual or multiple airway epithelial populations. Using these lines, we will examine the impact of the cellular pattern of ACE2 expression in the respiratory tract on the sequence of events following exposure to SARS-CoV2 coronavirus.