Diabetes induced by Coxsackie virus: Initiation by bystander damage and not molecular mimicry

Marc S. Horwitz, Linda M. Bradley, Judith Harbertson, Troy Krahl, Jae Lee, Nora Sarvetnick

Research output: Contribution to journalArticle

505 Citations (Scopus)

Abstract

Viral induction of autoimmunity is thought to occur by either bystander T-cell activation or molecular mimicry. Coxsackie B4 virus is strongly associated with the development of insulin-dependent diabetes mellitus in humans and shares sequence similarity with the islet autoantigen glutamic acid decarboxylase. We infected different strains of mice with Coxsackie B4 virus to discriminate between the two possible induction mechanisms, and found that mice with susceptible MHC alleles had no viral acceleration of diabetes, but mice with a T cell receptor transgene specific for a different islet autoantigen rapidly developed diabetes. These results show that diabetes induced by Coxsackie virus infection is a direct result of local infection leading to inflammation, tissue damage, and the release of sequestered islet antigen resulting in the re-stimulation of resting autoreactive T cells, further indicating that the islet antigen sensitization is an indirect consequence of the viral infection.

Original languageEnglish (US)
Pages (from-to)781-785
Number of pages5
JournalNature Medicine
Volume4
Issue number7
DOIs
StatePublished - Jul 1 1998

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Molecular Mimicry
Enterovirus
Medical problems
Viruses
Autoantigens
T-cells
Coxsackievirus Infections
T-Lymphocytes
Antigens
Glutamate Decarboxylase
Virus Diseases
T-Cell Antigen Receptor
Autoimmunity
Type 1 Diabetes Mellitus
Transgenes
Alleles
Inflammation
Chemical activation
Insulin
Tissue

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Diabetes induced by Coxsackie virus : Initiation by bystander damage and not molecular mimicry. / Horwitz, Marc S.; Bradley, Linda M.; Harbertson, Judith; Krahl, Troy; Lee, Jae; Sarvetnick, Nora.

In: Nature Medicine, Vol. 4, No. 7, 01.07.1998, p. 781-785.

Research output: Contribution to journalArticle

Horwitz, Marc S. ; Bradley, Linda M. ; Harbertson, Judith ; Krahl, Troy ; Lee, Jae ; Sarvetnick, Nora. / Diabetes induced by Coxsackie virus : Initiation by bystander damage and not molecular mimicry. In: Nature Medicine. 1998 ; Vol. 4, No. 7. pp. 781-785.
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