Antiviral immune responses: triggers of or triggered by autoimmunity?

Abstract

Viruses can serve as triggers of autoimmune disease by acting as adjuvants, leading to the priming of autoantigen-specific lymphocytes. Autoantigen-reactive T and B cells can also be activated following recognition of viral antigens with similarity to self antigens (molecular mimicry) or following recognition of new self epitopes released from damaged tissues (epitope spreading). Virus infection and immune control can also be altered, in terms of the type of immune response, the viral set point during chronic infections and the anatomical distribution of virus-specific lymphocytes, in patients with autoimmune diseases. Antiviral responses may be modified in these patients as a consequence of the same genetic variants that predispose them to autoimmune diseases. Dysregulated antiviral immune responses might reflect the contribution of these responses to autoimmune disease or might result from altered immune homeostasis in patients. Possible underlying mechanisms are discussed in the setting of autoimmune inflammation of the central nervous system. We focus on recent studies on the induction of immune-mediated demyelination by Theiler's murine encephalomyelitis virus infection and the association of multiple sclerosis with increased immune control of Epstein–Barr virus. An understanding of the underlying mechanisms of dysregulated virus-specific immune responses in autoimmune diseases could reveal new approaches for treating or diagnosing these diseases.