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Journal of Virology, October 2004, p. 11313-11320, Vol. 78, No. 20
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.20.11313-11320.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Coxsackievirus B4-Induced Cytokine Production in Pancreatic Cells Is Mediated through Toll-Like Receptor 4

Infection and Immunity Group, School of Life Sciences, University of Sussex, Falmer, Brighton, United Kingdom

Received 3 February 2004/ Accepted 6 June 2004

Coxsackievirus B4 (CBV4), a member of the Picornavirus genus, has long been implicated in the development of insulin-dependent diabetes mellitus (IDDM) caused by virus-induced pancreatic cell damage. The progressive destruction of pancreatic ß cells is responsible for the development of IDDM. It has recently been suggested that CBV4 infection can induce the production of proinflammatory cytokines, and these cytokines seem to be involved in the damage to the insulin-producing cells. In this study we investigated whether toll-like receptors (TLRs) are responsible for triggering the proinflammatory cytokine production in human pancreatic cells in response to CBV4. Here we demonstrate that CBV4 triggers cytokine production through a TLR4-dependent pathway. This interaction seems to be independent of virus attachment and cell entry.

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