Virus infection, antiviral immunity, and autoimmunity

Daniel R. Getts, Emily M.L. Chastain, Rachael L. Terry, Stephen D. Miller*

*Corresponding author for this work

Research output: Contribution to journalReview article

69 Scopus citations

Abstract

As a group of disorders, autoimmunity ranks as the third most prevalent cause of morbidity and mortality in the Western World. However, the etiology of most autoimmune diseases remains unknown. Although genetic linkage studies support a critical underlying role for genetics, the geographic distribution of these disorders as well as the low concordance rates in monozygotic twins suggest that a combination of other factors including environmental ones are involved. Virus infection is a primary factor that has been implicated in the initiation of autoimmune disease. Infection triggers a robust and usually well-coordinated immune response that is critical for viral clearance. However, in some instances, immune regulatory mechanisms may falter, culminating in the breakdown of self-tolerance, resulting in immune-mediated attack directed against both viral and self-antigens. Traditionally, cross-reactive T-cell recognition, known as molecular mimicry, as well as bystander T-cell activation, culminating in epitope spreading, have been the predominant mechanisms elucidated through which infection may culminate in an T-cell-mediated autoimmune response. However, other hypotheses including virus-induced decoy of the immune system also warrant discussion in regard to their potential for triggering autoimmunity. In this review, we discuss the mechanisms by which virus infection and antiviral immunity contribute to the development of autoimmunity.

Original languageEnglish (US)
Pages (from-to)197-209
Number of pages13
JournalImmunological Reviews
Volume255
Issue number1
DOIs
Publication statusPublished - Sep 1 2013

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Keywords

  • Autoimmune disease
  • Bystander activation
  • Epitope spreading
  • Microbial superantigens
  • Molecular mimicry
  • T-cell receptor affinity

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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