GSBS Student Publications

Title

Viral infection of engrafted human islets leads to diabetes

Student Author(s)

Glen Gallagher

GSBS Program

Immunology & Microbiology

UMMS Affiliation

Department of Medicine; Program in Molecular Medicine; Department of Quantitative Health Sciences

Date

4-2015

Document Type

Article

Medical Subject Headings

Animals; Coxsackievirus Infections; Diabetes Mellitus, Type 1; Enterovirus B, Human; Humans; Hyperglycemia; Islets of Langerhans; *Islets of Langerhans Transplantation; Mice

Disciplines

Endocrine System | Endocrine System Diseases | Immunology and Infectious Disease | Molecular Genetics

Abstract

Type 1 diabetes (T1D) is characterized by the destruction of the insulin-producing beta-cells of pancreatic islets. Genetic and environmental factors both contribute to T1D development. Viral infection with enteroviruses is a suspected trigger for T1D, but a causal role remains unproven and controversial. Studies in animals are problematic because of species-specific differences in host cell susceptibility and immune responses to candidate viral pathogens such as coxsackievirus B (CVB). In order to resolve the controversial role of viruses in human T1D, we developed a viral infection model in immunodeficient mice bearing human islet grafts. Hyperglycemia was induced in mice by specific ablation of native beta-cells. Human islets, which are naturally susceptible to CVB infection, were transplanted to restore normoglycemia. Transplanted mice were infected with CVB4 and monitored for hyperglycemia. Forty-seven percent of CVB4-infected mice developed hyperglycemia. Human islet grafts from infected mice contained viral RNA, expressed viral protein, and had reduced insulin levels compared with grafts from uninfected mice. Human-specific gene expression profiles in grafts from infected mice revealed the induction of multiple interferon-stimulated genes. Thus, human islets can become severely dysfunctional with diminished insulin production after CVB infection of beta-cells, resulting in diabetes. long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

Rights and Permissions

Citation: Diabetes. 2015 Apr;64(4):1358-69. doi: 10.2337/db14-1020. Epub 2014 Nov 12. Link to article on publisher's site

DOI of Published Version

10.2337/db14-1020

Related Resources

Link to Article in PubMed

Journal Title

Diabetes

PubMed ID

25392246