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Antiviral effect of nicotinamide on enterovirus‐infected human islets in vitro: Effect on virus replication and chemokine secretion
Author(s) -
Moëll Annika,
Skog Oskar,
Åhlin Erik,
Korsgren Olle,
Frisk Gun
Publication year - 2009
Publication title -
journal of medical virology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.782
H-Index - 121
eISSN - 1096-9071
pISSN - 0146-6615
DOI - 10.1002/jmv.21476
Subject(s) - coxsackievirus , nicotinamide , chemokine , virology , virus , viral replication , biology , lytic cycle , secretion , enterovirus , immune system , immunology , biochemistry , enzyme
Abstract Type 1 diabetes is a chronic disease characterized by the selective destruction of insulin‐producing cells in the pancreas. Enterovirus (EV) is the prime candidate to initiate this destruction and several inflammatory chemokines are induced by EV infection. Nicotinamide has been shown to protect isolated human islets, and to modulate chemokine expression. The aim of this study was to evaluate the effect of nicotinamide on EV replication and EV‐induced chemokine secretion and cytolysis of human islets. Two EV strains were used to infect human islets in vitro, one lytic (Adrian) isolated from a child at onset of type 1 diabetes, and one non‐lytic (VD2921). Secretion of the chemokines IP‐10 and MCP‐1, viral replication, and virus‐induced cytopathic effect (CPE), were measured at different time points post‐infection. Addition of nicotinamide to the culture medium reduced viral replication and virus‐induced islet destruction/CPE, significantly. Both EV strains increased secretion of IP‐10 and MCP‐1, when measured days 2–3, and days 5–7 post infection, compared to mock‐infected control islets. IP‐10 was not produced by uninfected isolated islets, whereas a basal secretion of MCP‐1 was detected. Interestingly, addition of nicotinamide blocked completely (Adrian), or reduced significantly (VD2921), the virus‐induced secretion of IP‐10. Secretion of MCP‐1 was also reduced in the presence of nicotinamide, from infected and uninfected islets. The reported antiviral effects of nicotinamide could have implications for the treatment/prevention of virus‐ and immune‐mediated disease. Also, this study highlights a possible mechanism of virus‐induced type 1 diabetes through the induction of MCP‐1 and IP‐10 in pancreatic islets. J. Med. Virol. 81:1082–1087, 2009. © 2009 Wiley‐Liss, Inc.