Enterovirus infection induces cytokine and chemokine expression in insulin-producing cells

J Med Virol. 2010 Nov;82(11):1950-7. doi: 10.1002/jmv.21900.


Despite evidence supporting an association between enterovirus (EV) infection and type 1 diabetes, the etiological mechanism(s) for EV-induced beta cell destruction is(are) not well understood. In this study, the effects of Coxsackievirus B (CVB) 1-6 on cell lysis and cytokine/chemokine expression in the insulinoma-1 (INS-1) beta cell line were investigated. Cytolysis was assessed using tissue culture infectious dose 50 (TCID(50)). Quantitative RT-PCR was used to measure viral RNA and mRNA of cytokines interferon (IFN)-α, IFN-β, IFN-γ, tumor necrosis factor (TNF)-α, and chemokine (C-X-C motif) ligand 10 (CXCL10), chemokine (C-C motif) ligand 2 (CCL2), and chemokine (C-C motif) ligand 5 (CCL5) in infected INS-1 cells. CVB2, 4, 5, and 6 lysed and replicated in INS-1 cells; TCID(50) was lowest for CVB5 and highest for CVB6. IFN-γ, CXCL10, and CCL5 mRNA levels all increased significantly following infection with CVB2, 4, 5, and 6 (P<0.05). CCL2 mRNA increased with CVB2, 5, and 6 (P<0.05), IFN-α mRNA increased with CVB5 infection (P<0.05), while TNF-α mRNA and IFN-β mRNA (P<0.001) increased with CVB2 infection. Dose-dependent effects of infection on cytokine mRNA levels were observed for all (P<0.01) except IFN-γ. Following inoculation of INS-1 cells with CVB1 and 3, viral RNA was not detected and cytokine/chemokine mRNA levels were unchanged. In conclusion, CVB2, 4, 5, and 6 induce dose-dependent cytokine and chemokine mRNA production from INS-1 cells suggesting that pro-inflammatory cytokine and chemokine secretion by beta cells is a potential mechanism for EV-induced beta cell damage in type 1 diabetes.

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Chemokine CXCL10 / metabolism
  • Chemokines / metabolism*
  • Chemokines, CC / metabolism
  • Cytokines / metabolism*
  • Diabetes Mellitus, Type 1 / immunology
  • Diabetes Mellitus, Type 1 / virology
  • Enterovirus B, Human / immunology*
  • Enterovirus B, Human / pathogenicity*
  • Humans
  • Inflammation / immunology*
  • Inflammation / metabolism
  • Insulin-Secreting Cells / immunology*
  • Insulin-Secreting Cells / metabolism*
  • Insulin-Secreting Cells / virology
  • Insulinoma / immunology
  • Insulinoma / metabolism
  • Insulinoma / virology
  • Interferons / metabolism
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Rats
  • Tumor Necrosis Factor-alpha / metabolism


  • Chemokine CXCL10
  • Chemokines
  • Chemokines, CC
  • Cytokines
  • RNA, Messenger
  • Tumor Necrosis Factor-alpha
  • Interferons