Tissue-specific deletion of the coxsackievirus and adenovirus receptor protects mice from virus-induced pancreatitis and myocarditis.
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.
Kallewaard
Nicole L
NL
Division of Infectious Diseases, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
Zhang
Lili
L
Chen
Jin-Wen
JW
Guttenberg
Marta
M
Sanchez
Melissa D
MD
Bergelson
Jeffrey M
JM
D000818:Animals; D002478:Cells, Cultured; D000090702:Constitutive Androstane Receptor; D003384:Coxsackievirus Infections / Q000517:prevention & control*; D017353:Gene Deletion; D006321:Heart / Q000821:virology; D051379:Mice; D018345:Mice, Knockout; D009205:Myocarditis / Q000517:prevention & control* / Q000821:virology; D009206:Myocardium / Q000473:pathology; D010179:Pancreas / Q000473:pathology / Q000821:virology; D010195:Pancreatitis / Q000517:prevention & control* / Q000821:virology; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics*
D000090702:Constitutive Androstane Receptor; D018160:Receptors, Cytoplasmic and Nuclear