Diabetogenic potential of human pathogens uncovered in experimentally permissive β-cells

Malin Flodström, Devin Tsai, Cody Fine, Amy Maday, Nora Sarvetnick

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

Pancreatic β-cell antiviral defense plays a critical role in protection from coxsackievirus B4 (CVB4)-induced diabetes. In the present study, we tested the hypothesis that interferon (IFN)-induced antiviral defense determines β-cell survival after infection by the human pathogen CVB3, cytomegalovirus (CMV), and lymphocytic choriomeningitis virus (LCMV). We demonstrated that mice harboring β-cells that do not respond to IFN because of the expression of the suppressor of cytokine signaling-1 (SOCS-1) succumb to an acute form of type 1 diabetes after infection with CVB3. Interestingly, the tropism of the virus was altered in SOCS-1 transgenic (Tg) mice, and CVB3 was detected in islet cells of SOCS-1-Tg mice before β-cell loss and the onset of diabetes. Furthermore, insulitis was increased in SOCS1-Tg mice after infection with murine CMV, and a minority of the mice developed overt diabetes. However, infection with LCMV failed to cause β-cell destruction in SOCS-1 Tg mice. These findings suggest that CVB3 can cause diabetes in a host lacking adequate β-cell antiviral defense, and that incomplete target cell antiviral defense may enhance susceptibility to diabetes triggered by CMV. In conclusion, suppressed β-cell antiviral defense reveals the diabetogenic potential of two pathogens previously linked to the onset of type 1 diabetes in humans.

Original languageEnglish (US)
Pages (from-to)2025-2034
Number of pages10
JournalDiabetes
Volume52
Issue number8
DOIs
StatePublished - Aug 1 2003

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Antiviral Agents
Transgenic Mice
Cytokines
Lymphocytic choriomeningitis virus
Infection
Cytomegalovirus
Type 1 Diabetes Mellitus
Interferons
Muromegalovirus
Tropism
Enterovirus
Islets of Langerhans
Cell Survival
Viruses

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

Diabetogenic potential of human pathogens uncovered in experimentally permissive β-cells. / Flodström, Malin; Tsai, Devin; Fine, Cody; Maday, Amy; Sarvetnick, Nora.

In: Diabetes, Vol. 52, No. 8, 01.08.2003, p. 2025-2034.

Research output: Contribution to journalArticle

Flodström, Malin ; Tsai, Devin ; Fine, Cody ; Maday, Amy ; Sarvetnick, Nora. / Diabetogenic potential of human pathogens uncovered in experimentally permissive β-cells. In: Diabetes. 2003 ; Vol. 52, No. 8. pp. 2025-2034.
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