Viral Infections and Autoimmune Disease: Roles of LCMV in Delineating Mechanisms of Immune Tolerance

Abstract

Viral infections are a natural part of our existence. They can affect us in many ways that are the result of the interaction between the viral pathogen and our immune system. Most times, the resulting immune response is beneficial for the host. The pathogen is cleared, thus protecting our vital organs with no other consequences. Conversely, the reaction of our immune system against the pathogen can cause organ damage (immunopathology) or lead to autoimmune disease. To date, there are several mechanisms for virus-induced autoimmune disease, including molecular mimicry and bystander activation, in support of the "fertile field" hypothesis (terms defined in our review). In contrast, viral infections have been associated with protection from autoimmunity through mechanisms that include Treg invigoration and immune deviation, in support of the "hygiene hypothesis", also defined here. Infection with lymphocytic choriomeningitis virus (LCMV) is one of the prototypes showing that the interaction of our immune system with viruses can either accelerate or prevent autoimmunity. Studies using mouse models of LCMV have helped conceive and establish several concepts that we now know and use to explain how viruses can lead to autoimmune activation or induce tolerance. Some of the most important mechanisms established during the course of LCMV infection are described in this short review.

Keywords: autoimmunity; bystander activation; immune tolerance; lymphocytic choriomeningitis virus (LCMV); molecular mimicry; viral infection.

Figure 1

Lymphocytic choriomeningitis virus (LCMV) infection can induce tolerance and promote autoimmunity via mechanisms that include antigen-specific tolerance, immune suppression (death of autoreactive T cells) Treg invigoration, and immune deviation via chemokine gradients (e.g., CXCL10). In contrast, virus infection can initiate or propagate an autoimmune disease via epitope spreading and molecular mimicry, inflammation, and activation of antigen-presenting cells (APCs) that present self-antigens.