Enterovirus Infection Induces Cytokine and Chemokine Expression in Insulin-Producing Cells

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 (TCID50). Quantitative RT-PCR was used tomeasure viral RNA and mRNA of cytokines interferon (IFN)-alpha, IFN-beta, IFN-gamma, tumor necrosis factor (TNF)-alpha, 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; TCID50 was lowest for CVB5 and highest for CVB6. IFN-gamma, 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-alpha mRNA increased with CVB5 infection (P<0.05), while TNF-alpha mRNA and IFN-beta mRNA (P<0.001) increased with CVB2 infection. Dose-dependent effects of infection oncytokine mRNA levels were observed for all (P<0.01) except IFN-gamma. 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. J. Med. Virol. 82: 1950-1957, 2010. (C) 2010 Wiley-Liss, Inc.