DEVELOPMENTAL EXPRESSION OF COXSACKIE ADENOVIRUS RECEPTOR

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 柯萨奇病毒B和腺病毒是与人类心肌炎发展有关的最常见病毒病原体，并通过科萨基腺病毒受体（CAR）进入细胞。 我们使用RT-PCR、免疫印迹和免疫荧光检查了非人灵长类动物中的CAR表达。 这些数据表明，心肌炎和新生儿CVB感染的其他表现可能反映了较高的CAR表达。 在8只食蟹猴中获得基线ECG、柯萨奇病毒抗体水平和超声心动图。 微创心脏活检技术的初步培训已经完成。 最初，用108 pfu的柯萨奇病毒IV接种两只猴子。 两只动物均显示出疾病的临床体征，并在多个器官中有病毒诱导病变的组织学证据。 由于最初的感染引起了如此严重的急性感染，接下来的两只动物接受了减少剂量的病毒。 一只接受IV接种，另一只接受经口/胃暴露。 两只动物都被感染，但经口接种的动物似乎在2周内清除了感染。 第三对动物接受107 pfu科萨基病毒的IV接种，并在接种后4周跟踪病毒血症和心脏病变的发展。 最后两只猴子的接种将在接下来的几周内进行，等待最后两只动物的病毒学和病理学结果。 目前的结果表明，食蟹猴是一个有用的模型，科萨基病毒感染的人。

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, two monkeys were inoculated IV with 108 pfu of cocsackie virus. Both animals showed clinical signs of disease and had histologic evidence of virus-induced lesions in multiple organs. Because the initial infection caused such a severe, acute infection the next two animals received a reduced dose of virus. On was inoculated IV and the second received an oral/gastric exposure. Both animals became infected but the orally inoculated animal appeared to clear the infection within 2 weeks. The third pair of animals received an IV inoculation of 107 pfu of coxsackie virus and were followed for virema and development of cardiac lesions for 4 weeks post-inoculation. Inoculation of the final two monkeys will occur in the next few weeks pending virology and pathology results from the last two animals. Current results indicate that cynomolgus macaques are a useful model of coxsackie virus infection in humans.