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Enterovirus-induced gene expression profile is critical for human pancreatic islet destruction
Intestinal Viruses Unit, National Intestinal Viruses Unit, National Institute for Health and Welfare (THL), Helsinki, Finland.
Intestinal Viruses Unit, National Institute for Health and Welfare (THL), Helsinki, Finland.
VTT Technical Research Center of Finland, Espoo, Finland.
Intestinal Viruses Unit, National Institute for Health and Welfare (THL), Helsinki, Finland.
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2012 (English)In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 55, no 12, p. 3273-3283Article in journal (Refereed) Published
Abstract [en]

AIMS/HYPOTHESIS: Virally induced inflammatory responses, beta cell destruction and release of beta cell autoantigens may lead to autoimmune reactions culminating in type 1 diabetes. Therefore, viral capability to induce beta cell death and the nature of virus-induced immune responses are among key determinants of diabetogenic viruses. We hypothesised that enterovirus infection induces a specific gene expression pattern that results in islet destruction and that such a host response pattern is not shared among all enterovirus infections but varies between virus strains.

METHODS: The changes in global gene expression and secreted cytokine profiles induced by lytic or benign enterovirus infections were studied in primary human pancreatic islet using DNA microarrays and viral strains either isolated at the clinical onset of type 1 diabetes or capable of causing a diabetes-like condition in mice.

RESULTS: The expression of pro-inflammatory cytokine genes (IL-1-α, IL-1-β and TNF-α) that also mediate cytokine-induced beta cell dysfunction correlated with the lytic potential of a virus. Temporally increasing gene expression levels of double-stranded RNA recognition receptors, antiviral molecules, cytokines and chemokines were detected for all studied virus strains. Lytic coxsackievirus B5 (CBV-5)-DS infection also downregulated genes involved in glycolysis and insulin secretion.

CONCLUSIONS/INTERPRETATION: The results suggest a distinct, virus-strain-specific, gene expression pattern leading to pancreatic islet destruction and pro-inflammatory effects after enterovirus infection. However, neither viral replication nor cytotoxic cytokine production alone are sufficient to induce necrotic cell death. More likely the combined effect of these and possibly cellular energy depletion lie behind the enterovirus-induced necrosis of islets.

Place, publisher, year, edition, pages
Springer, 2012. Vol. 55, no 12, p. 3273-3283
National Category
Gastroenterology and Hepatology
Identifiers
URN: urn:nbn:se:oru:diva-63673DOI: 10.1007/s00125-012-2713-zISI: 000310381800016PubMedID: 22983635Scopus ID: 2-s2.0-84868199568OAI: oai:DiVA.org:oru-63673DiVA, id: diva2:1169237
Note

Funding agencies:

Juvenile Diabetes Research Foundation (USA)

European Union EP7-HEALTH-2007 DIA-PREPP N202013

Academy of Finland

Paivikki and Sakari Sohlberg Foundation

Finnish Diabetes Foundation

Maud Kuistila Memorial Foundation

Available from: 2017-12-22 Created: 2017-12-22 Last updated: 2018-05-15Bibliographically approved

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Oresic, Matej

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