Yanagawa Bobby, Spiller O Brad, Proctor David G, Choy Jonathan, Luo Honglin, Zhang Huifang M, Suarez Agripina, Yang Decheng, McManus Bruce M
The James Hogg iCAPTURE Centre for Cardiovascular and Pulmonary Research, Department of Pathology and Laboratory Medicine, St. Paul's Hospital/Providence Health Care-UBC, Vancouver, Canada.
J Infect Dis. 2004 Apr 15;189(8):1431-9. doi: 10.1086/382598. Epub 2004 Apr 5.
Group B coxsackievirus infection can result in organ injury and inflammation. The coxsackievirus and adenovirus receptor (CAR) and decay-accelerating factor (DAF; CD55) have both been identified as receptors for coxsackievirus B3 (CVB3). We have shown elsewhere that early DAF-Fc treatment attenuates CVB3-induced myocarditis and virus replication.
CAR was synthesized as a soluble IgG1-Fc fusion protein (CAR-Fc). In vitro, CAR-Fc blocked infection by 2 different strains of CVB3. A/J mice were infected in vivo with CVB3 and were administered CAR-Fc either 3 days before infection, during infection, or 3 days after infection and were compared with mice infected with virus alone and control animals.
All CAR-Fc treatment groups had reduced recoverable infectious virus in the heart. CAR-Fc treatment of mice, either preceding or concurrent with CVB3 infection, resulted in complete inhibition of myocardial lesion area, cell death and inflammation, and viral RNA. Early treatment also completely blocked inflammation and cell death in the pancreas, an organ that is normally very sensitive to infection.
To our knowledge, CAR-Fc is the only protein that has been shown to block coxsackievirus infection of the pancreas. However, regardless of the efficacy of the test protein, target tissue cannot be rescued after day 3 of infection in the A/J mouse model.
B组柯萨奇病毒感染可导致器官损伤和炎症。柯萨奇病毒和腺病毒受体（CAR）以及衰变加速因子（DAF；CD55）均已被确定为柯萨奇病毒B3（CVB3）的受体。我们在其他地方已经表明，早期给予DAF-Fc治疗可减轻CVB3诱导的心肌炎和病毒复制。
将CAR合成为可溶性IgG1-Fc融合蛋白（CAR-Fc）。在体外，CAR-Fc可阻断两种不同CVB3毒株的感染。将A/J小鼠体内感染CVB3，并在感染前3天、感染期间或感染后3天给予CAR-Fc，然后将其与仅感染病毒的小鼠和对照动物进行比较。
所有CAR-Fc治疗组心脏中可恢复的感染性病毒均减少。在CVB3感染之前或同时对小鼠进行CAR-Fc治疗，可完全抑制心肌病变面积、细胞死亡和炎症以及病毒RNA。早期治疗还完全阻断了胰腺中的炎症和细胞死亡，胰腺是一个通常对感染非常敏感的器官。
据我们所知，CAR-Fc是唯一已被证明可阻断胰腺柯萨奇病毒感染的蛋白质。然而，在A/J小鼠模型中，无论测试蛋白的疗效如何，在感染后第3天之后靶组织都无法恢复。
