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

Cell Host Microbe. 2009 Jul 23;6(1):91-8. doi: 10.1016/j.chom.2009.05.018.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cells, Cultured
  • 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*

Substances

  • Receptors, Cytoplasmic and Nuclear
  • constitutive androstane receptor