Analysis of the relationship between viral infection and autoimmune disease

The clinical association between viral infection and onset or exacerbation of autoimmune disorders remains poorly understood. Here, we examine the rel ative roles of molecular mimicry and nonspecific inflammatory stimuli in pr ogression from infection to autoimmune disease. Murine herpes virus 1 (HSV- 1 KOS) infection triggers T cell-dependent autoimmune reactions to corneal tissue. We generated an HSV-1 KOS point mutant containing a single amino ac id exchange within the putative mimicry epitope as well as mice expressing a TOR transgene specific for the self-peptide mimic to allow dissection of two pathogenic mechanisms in disease induction. These experiments indicate that viral mimicry is essential for disease induction after low-level viral infection of animals containing limited numbers of autoreactive T cells, w hile innate immune mechanisms become sufficient to provoke disease in anima ls containing relatively high numbers of autoreactive T cells.