Coxsackievirus infection of the pancreas: evaluation of receptor expression, pathogenesis, and immunopathology

Virology. 2000 Jun 5;271(2):276-88. doi: 10.1006/viro.2000.0332.

Abstract

Coxsackievirus type B (CVB) infection of the pancreas induces a massive cellular infiltrate composed of natural killer cells, T cells, and macrophages and leads to the destruction of exocrine tissue. The physiological manifestations of pancreatic CVB infection are correlated with viral tropism; the virus infects acinar cells but spares the islets of Langerhans. Here we evaluate the mechanisms underlying pancreatic inflammation and destruction and identify the determinants of viral tropism. T-cell-mediated immunopathology has been invoked, along with direct virus-mediated cytopathicity, to explain certain aspects of CVB-induced pancreatic disease. However, we show here that in the pancreas, the extent of inflammation and tissue destruction appears unaltered in the absence of the cytolytic protein perforin; these findings exclude any requirement for perforin-mediated lysis by natural killer cells or cytotoxic T cells in CVB3-induced pancreatic damage. Furthermore, perforin-mediated cytotoxic T-cell activity does not contribute to the control of CVB infection in this organ. In addition, we demonstrate that the recently identified coxsackie-adenovirus receptor is expressed at high levels in acinar cells but is barely detectable in islets, which is consistent with its being a major determinant of virus tropism and, therefore, of disease. However, further studies using various cell lines of pancreatic origin reveal secondary determinants of virus tropism.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • CD55 Antigens / genetics
  • Coxsackie and Adenovirus Receptor-Like Membrane Protein
  • Coxsackievirus Infections / immunology
  • Coxsackievirus Infections / pathology
  • Coxsackievirus Infections / virology*
  • Enterovirus B, Human / immunology
  • Enterovirus B, Human / metabolism
  • Enterovirus B, Human / pathogenicity*
  • Gene Expression
  • HeLa Cells
  • Humans
  • Killer Cells, Natural / immunology
  • Male
  • Membrane Glycoproteins / immunology
  • Mice
  • Mice, Inbred C57BL
  • Pancreas / cytology
  • Pancreas / immunology
  • Pancreas / pathology
  • Pancreas / virology*
  • Perforin
  • Pore Forming Cytotoxic Proteins
  • RNA, Viral / biosynthesis
  • Receptors, Virus / genetics*
  • T-Lymphocytes, Cytotoxic / immunology
  • Tissue Distribution
  • Transfection
  • Tumor Cells, Cultured

Substances

  • CD55 Antigens
  • CLMP protein, human
  • CLMP protein, mouse
  • Coxsackie and Adenovirus Receptor-Like Membrane Protein
  • Membrane Glycoproteins
  • Pore Forming Cytotoxic Proteins
  • RNA, Viral
  • Receptors, Virus
  • Perforin