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

Abstract

Viral infections make a natural part of our existence. They can affect us in hundreds of different 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 gets cleared protecting our vital organs with no other consequences. Sometimes, things go wrong and the reaction of our immune system against the pathogen causes organ damage (immunopathology) or leads 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. On the flip side, viral infections have been associated with protection from autoimmunity through mechanisms that include Treg invigoration and immune deviation, in support of the “hygiene hypothesis”. Infection with lymphocytic choriomeningitis virus (LCMV) is one of the prototype viral systems showing that the interaction of our immune system with the viruses can either accelerate or prevent autoimmunity. Studies using LCMV have helped conceive and establish several concepts that we today know and explain how viruses can lead to autoimmune activation or induce tolerance. Some of the most important mechanisms established in LCMV are described in this short review.

Regulatory functions of NK cells during infections and cancer

“…Studies using lymphocytic choriomeningitis virus (LCMV) infection unraveled that NK cells can negatively regulate the magnitude of the antiviral response. LCMV constitutes an excellent experimental model that has been widely used to address tissue‐specific tolerance and its underlying mechanisms 40,41 . Although LCMV infection strongly activates NK cells, virus elimination is NK cell‐independent 42 .…”

“…LCMV constitutes an excellent experimental model that has been widely used to address tissue-specific tolerance and its underlying mechanisms. 40,41 Although LCMV infection strongly activates NK cells, virus elimination is NK cell-independent. 42 Besides, in 2B4-deficient LCMV-infected mice, NK cells were able to eliminate activated CD8 T cells in vitro and in vivo, suggesting that 2B4-CD48 interactions protects CD8 T cells from NK cell-mediated killing during viral infection.…”

Neuropathogenesis of Neurotropic Viruses

“…It has been established in experimental model that viral inoculation into the CNS result into activation of CD8+ T cell mediated inflammatory response inside the virus-infected CNS that mediates destruction of the blood-brain and blood-CSF barriers [26]. This responses were shown to be mediated by T cell recognition of its target via major histocompatibility (MCH) class I and II molecules, and consequently produce severe inflammation of the leptomeniges, the choroid plexus and the ependyma lining the ventricles with partial sparing of the brain parenchyma and the cellular infiltrates seen were macrophages and CD8+ T lymphocytes, which is mainly virus-specific CD8+ T cells constituting about 90% [26,27,28,29].…”