Development of the ferret model for EV-D68 infection

摘要 急性弛缓性肌无力（AFM）是一种使幼儿衰弱的疾病。AFM的确切原因是目前 尽管EV-D 68未知，但肠道病毒已与AFM暂时相关。确切的机制是 EV-D 68引起脊髓和CNS病变的机制尚不清楚。在这里，我们建议发展 免疫活性小动物模型，即雪貂，用于研究EV-D 68感染。雪貂已经 广泛用作研究呼吸道病原体如流感、RSV、SARS、Hendra和Nipah的模型 病毒鉴于下呼吸道是EV-D 68的主要进入途径，我们假设， 雪貂将作为研究EV-D 68发病机制的可行模型。在目标1中，我们将开发 鼻内感染，并描绘相关的发病机制和免疫，并在目标2，我们将制定一个 新的禽副粘病毒的EV-D 68疫苗，以检查其预防鼻内攻击的潜力。 这些研究将为EV-D 68的发病机制和疫苗介导的免疫应答机制提供新的见解。 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.