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Interferons induce an antiviral state in human pancreatic islet cells
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Clinical Immunology.
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2007 (English)In: Virology, ISSN 0042-6822, E-ISSN 1096-0341, Vol. 367, no 1, 92-101 p.Article in journal (Refereed) Published
Abstract [en]

Enterovirus infections, in particular those with Coxsackieviruses, have been linked to the development of type 1 diabetes (T1D). Although animal models have demonstrated that interferons (IFNs) regulate virus-induced T1D by acting directly on the beta cell, little is known on the human pancreatic islet response to IFNs. Here we show that human islet cells respond to IFNs by expressing signature genes of antiviral defense. We also demonstrate that they express three intracellular sensors for viral RNA, the toll like receptor 3 (TLR3) gene, the retinoic acid-inducible gene I (RIG-I) and the melanoma differentiation-associated gene-5 (MDA-5), which induce type I IFN production in infected cells. Finally, we show for the first time that the IFN-induced antiviral state provides human islets with a powerful protection from the replication of Coxsackievirus. This may be critical for beta cell survival and protection from virus-induced T1D in humans.

Place, publisher, year, edition, pages
2007. Vol. 367, no 1, 92-101 p.
Keyword [en]
Beta cell biology, Chemokine(s), Enterovirus, Human islets, IFN-gamma, Infection, Innate immunity type 1, IP-10, Microarray analysis
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:uu:diva-103616DOI: 10.1016/j.virol.2007.05.010ISI: 000249902500010PubMedID: 17559902OAI: oai:DiVA.org:uu-103616DiVA: diva2:218576
Available from: 2009-05-20 Created: 2009-05-20 Last updated: 2011-01-26Bibliographically approved

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