Rat pancreatic beta cells and cytomegalovirus infection

Maaike J Smelt, Marijke M Faas, Bart J de Haan, Jeroen Hofstede, Chi-Wai Cheung, Hanna van der Iest, Aalzen de Haan, Paul de Vos

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Objectives: Cytomegalovirus (CMV) infection has been suggested to accelerate β-cell destruction and thereby to contribute to new-onset diabetes and failure of islet allografts in both humans and rodents. Surprisingly, direct CMV infection of β cells has received only minor attention. Therefore, we investigated the susceptibility of rat β cells for rat CMV (RCMV) infection and the direct effects on the regulation of immune cell-activating ligands. Methods: Primary rat β cells, the rat β-cell line Rin-m5F, and fibroblasts were RCMV-infected in vitro. The viral gene and protein expression levels were determined as a measure for RCMV susceptibility. Gene expression levels of intracellular adhesion molecule 1, lymphocyte function associated antigen 3, rat major histocompatibility complex region A, rat major histocompatibility complex region E, toll like receptor 2, and clustered domain 14 were determined as a measure for cellular immunogenicity. Results: We demonstrate that β cells are susceptible for RCMV infection but allow only low levels of viral gene expression. In contrast, infected fibroblasts demonstrated productive viral infection and formation of viral progeny. After RCMV infection, β-cell immunogenicity was markedly increased, as demonstrated by the increased cellular expression of immune cell-activating ligands. Conclusions: Direct β-cell infection by RCMV and subsequent low-grade viral gene expression may lead to increased immunogenicity of native or transplanted β cells in vivo. An infection-induced enhanced β-cell recognizability may have important consequences for β-cell survival and the development of diabetes or rejection of islet grafts. Copyright © 2009 by Lippincott Williams & Wilkins.
Original languageEnglish
Pages (from-to)47-56
JournalPancreas
Volume39
Issue number1
DOIs
Publication statusPublished - Jan 2010
Externally publishedYes

Keywords

  • Animals
  • Blotting, Western
  • CD58 Antigens/genetics
  • Cell Line, Tumor
  • Cells, Cultured
  • Cytomegalovirus/genetics
  • Cytomegalovirus Infections/genetics
  • Disease Models, Animal
  • Fibroblasts/metabolism
  • Flow Cytometry
  • Gene Expression
  • Histocompatibility Antigens/genetics
  • Host-Pathogen Interactions
  • Insulin-Secreting Cells/metabolism
  • Intercellular Adhesion Molecule-1/genetics
  • Lipopolysaccharide Receptors/genetics
  • Microscopy, Electron
  • Rats
  • Reverse Transcriptase Polymerase Chain Reaction
  • Toll-Like Receptor 2/genetics
  • Viral Proteins/genetics

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  • Cite this

    Smelt, M. J., Faas, M. M., de Haan, B. J., Hofstede, J., Cheung, C-W., van der Iest, H., de Haan, A., & de Vos, P. (2010). Rat pancreatic beta cells and cytomegalovirus infection. Pancreas, 39(1), 47-56. https://doi.org/10.1097/MPA.0b013e3181bab120