Development of the ferret model for EV-D68 infection

摘要 急性松弛性脊髓炎(AFM)是一种使幼儿虚弱的疾病。原子力显微镜的确切原因是目前 虽然EV-D68病毒未知，但已有一种肠道病毒与AFM暂时联系在一起。确切的机制是 EV-D68通过这种病毒引起脊髓和中枢神经系统的病理尚不清楚。在这里，我们建议开发 一种免疫活性小动物模型，即研究EV-D68感染的雪貂。雪貂已经被 广泛用于研究呼吸道病原体，如流感、RSV、SARS、Hendra和Nipah 病毒。鉴于下呼吸道是EV-D68的主要进入途径，我们假设 雪貂将成为研究EV-D68致病机理的可行模型。在目标1中，我们将开发以下模型 鼻腔感染，并勾勒出发病机制和免疫的相关性，在目标2中，我们将开发一种 基于新型禽副粘病毒的EV-D68疫苗研究其预防鼻腔攻击的潜力。 这些研究将为EV-D68致病机制和疫苗介导的研究提供新的见解。 防止呼吸道感染。

ABSTRACT Acute Flaccid Myelitis (AFM) is a debilitating condition in young children. The exact cause of AFM is currently unknown though EV-D68, an enterovirus has been temporally associated with AFM. The exact mechanism's by which EV-D68 causes spinal cord and CNS pathology is not known. Here we propose the development of an immunocompetent small animal model, namely the ferret to study EV-D68 infections. Ferrets have been widely used as a model to study respiratory pathogens such as influenza, RSV, SARS, Hendra and Nipah viruses. Given that the lower respiratory tract is the primary route of entry for EV-D68, we hypothesize that ferrets will serve as a viable model to study EV-D68 pathogenesis. In aim 1, we will develop the model of intranasal infection and delineate the correlates of pathogenesis and immunity, and in aim 2 we will develop a novel avian paramyxovirus based EV-D68 vaccine to examine its potential to prevent intranasal challenge. These studies will provide novel insights into the mechanisms of EV-D68 pathogenesis and vaccine mediated protection from respiratory infections.