Tissue-specific deletion of the coxsackievirus and adenovirus receptor protects mice from virus-induced pancreatitis and myocarditis

• Published in: Cell host & microbe Vol. 6; no. 1; pp. 91 - 98
• Main Authors: Kallewaard, Nicole L, Zhang, Lili, Chen, Jin-Wen, Guttenberg, Marta, Sanchez, Melissa D, Bergelson, Jeffrey M
• Format: Journal Article
• Language: English
• Published: United States 23.07.2009
• Subjects: Animals; Cells, Cultured; Constitutive Androstane Receptor; Coxsackievirus Infections - prevention & control; Gene Deletion; Heart - virology; Mice; Mice, Knockout; Myocarditis - prevention & control; Myocarditis - virology; Myocardium - pathology; Pancreas - pathology; Pancreas - virology; Pancreatitis - prevention & control; Pancreatitis - virology; Receptors, Cytoplasmic and Nuclear - genetics
• ISSN: 1931-3128; 1934-6069
• DOI: 10.1016/j.chom.2009.05.018

In cultured cells, infection by group B coxsackievirus (CVB) is mediated by the coxsackievirus and adenovirus receptor (CAR), but the importance of this molecule in CVB-induced disease has not been determined. We generated mice with tissue-specific ablation of CAR within each of two major CVB target organs, the pancreas and heart. In the pancreas, deletion of CAR resulted in a significant reduction in both virus titers and virus-induced tissue damage. Similarly, cardiomyocyte-specific CAR deletion resulted in a marked reduction in virus titer, infection-associated cytokine production, and histopathology within the heart. Consistent with the in vivo phenotype, CAR-deficient cardiomyocytes resisted infection in vitro. These results demonstrate a critical function for CAR in the pathogenesis of CVB infection in vivo and in virus tropism for the heart and pancreas.