DEVELOPMENTAL EXPRESSION OF COXSACKIE ADENOVIRUS RECEPTOR

柯萨奇腺病毒受体的发育表达

• 批准号: 7562311
• 负责人: PAUL A KROGSTAD
• 金额: $ 1.4万
• 依托单位: TULANE UNIVERSITY OF LOUISIANA
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-05-01 至 2008-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7562311
• 关键词: Acute; Adenoviruses; Animals; Antibodies; Biopsy; CAR receptor; Cardiac; Cells; Clinical; Computer Retrieval of Information on Scientific Projects Database; Coxsackie B Viruses; Coxsackie Viruses; Coxsackievirus Infections; Data; Development; Disease; Dose; Echocardiography; Electrocardiogram; Funding; Grant; Histologic; Human; Human Development; Immunoblotting; Immunofluorescence Immunologic; Infection; Institution; Invasive; Lesion; Macaca; Macaca fascicularis; Modeling; Monkeys; Myocarditis; Newborn Infant; Oral; Organ; Pathology; Polymerase Chain Reaction; Research; Research Personnel; Resources; Source; Stomach; Techniques; Training; United States National Institutes of Health; Viral; Virus; Week; nonhuman primate; pathogen; receptor expression; virology

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.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目和 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 柯萨奇 B 型病毒和腺病毒是与人类心肌炎的发展有关的最常见的病毒病原体，并通过柯萨奇腺病毒受体 (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。 这些数据表明新生儿的心肌炎和CVB感染的其他表现可能反映了较高的CAR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，两只猴子静脉注射 108 pfu 的柯萨奇病毒。 两只动物均表现出疾病的临床症状，并具有病毒引起的多个器官病变的组织学证据。 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。 第一个接受静脉注射，第二个接受口腔/胃接触。 两只动物都被感染，但口服接种的动物似乎在两周内清除了感染。 第三对动物接受 107 pfu 柯萨奇病毒的静脉注射，并在接种后 4 周内追踪病毒感染和心脏病变的发展情况。 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，食蟹猴是人类柯萨奇病毒感染的有用模型。