DEVELOPMENTAL EXPRESSION OF COXSACKIE ADENOVIRUS RECEPTOR

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 柯萨奇B组病毒和腺病毒是与人类心肌炎发生发展有关的最常见的病毒病原体，它们通过柯萨奇病毒受体(CAR)进入细胞。我们使用RT-PCR、免疫印迹和免疫荧光检测了非人类灵长类动物中CAR的表达。这些数据表明，新生儿CVB感染的心肌炎和其他表现可能反映了CAR的高表达。对8只食蟹猴进行了基线心电图、柯萨奇病毒抗体水平和超声心动图检查。微创心脏活检技术的初步培训已经完成。最初，五只猴子接种了IV疫苗，一只猴子口服接种了柯萨奇病毒。初步结果表明，猴子通过两种途径感染，静脉接种的动物病毒载量较高。研究的最后三只猴子被静脉接种一种从一名严重心肌炎患者的心肌中分离出来的柯萨奇B病毒株。该菌株在体外培养，并通过超声心动图评估引起急性心肌变化。目前的研究结果表明，食蟹猴是人类感染柯萨奇病毒的有用模型。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Coxsackievirus B and Adenoviruses are the most common viral pathogens implicated in the development of human myocarditis, and gain entry into cells via the Coxsackie Adenovirus Receptor (CAR). We examined CAR expression in non-human primates, using RT- PCR, immunoblot, and immunofluorescence. These data suggest indicate that myocarditis and other manifestations of CVB infection in newborns may reflect higher CAR expression. Baseline ECG, antibody levels to coxsackievirus, and echocardiograms were obtained in 8 cynomolgus monkeys. Initial training for minimally invasive cardiac biopsy techniques has been completed. Initially, five monkeys were inoculated IV and one monkey was inoculated orally with cocsackievirus. Preliminary results indicated that the monkeys became infected by both routes, with higher viral loads in IV inoculated animals. The final three monkeys of the study were inoculated IV with a strain of coxsackievirus B isolated from the myocardium of a human patient with severe myocarditis. This strain was cultured in vitro and caused acute myocardial changes as assessed by echocardiography. Current results indicate that cynomolgus macaques are a useful model of coxsackie virus infection in humans.