Soluble Recombinant Coxsackievirus and Adenovirus Receptor Abrogates Coxsackievirus B3-Mediated Pancreatitis and Myocarditis in Mice

• Published in: The Journal of infectious diseases 2004-04, Vol.189 (8), p.1431-1439
• Main Authors: Yanagawa, Bobby, Spiller, O. Brad, Proctor, David G., Choy, Jonathan, Luo, Honglin, Zhang, Huifang M., Suarez, Agripina, Yang, Decheng, McManus, Bruce M.
• Format: Article
• Language: English
• Subjects: Adenoviruses; Animals; Biological and medical sciences; Coxsackie and Adenovirus Receptor-Like Membrane Protein; Coxsackievirus B3; Coxsackievirus Infections - drug therapy; Coxsackievirus Infections - immunology; Coxsackievirus Infections - pathology; Cytopathogenic Effect, Viral - immunology; Enterovirus; Enterovirus B, Human - genetics; Enterovirus B, Human - immunology; Fundamental and applied biological sciences. Psychology; Histocytochemistry; In Situ Hybridization; Infections; Infectious diseases; Kidney - virology; Liver - virology; Male; Medical sciences; Mice; Microbiology; Miscellaneous; Myocarditis; Myocarditis - drug therapy; Myocarditis - virology; Neutralization Tests; Pancreas; Pancreatitis; Pancreatitis - drug therapy; Pancreatitis - virology; Random Allocation; Receptors; Receptors, Virus - immunology; Receptors, Virus - physiology; Recombinant Proteins - immunology; Recombinant Proteins - pharmacology; Spleen - virology; Tissue samples; Virology; Virus Replication - immunology; Viruses
• ISSN: 0022-1899; 1537-6613
• DOI: 10.1086/382598

Background. 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. Methods. 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 CARFc either 3 days before infection, during infection, or 3 days after infection and were compared with mice infected with virus alone and control animals. Results. 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. Conclusion. 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.