Experimental encephalomyelitis at age 90, still relevant and elucidating how viruses trigger disease

20 yr ago, a tribute appeared in this journal on the 70th anniversary of an animal model of disseminated encephalomyelitis, abbreviated EAE for experimental autoimmune encephalomyelitis. "Observations on Attempts to Produce Disseminated Encephalomyelitis in Monkeys" appeared in the Journal of Experimental Medicine on February 21, 1933. Rivers and colleagues were trying to understand what caused neurological reactions to viral infections like smallpox, vaccinia, and measles, and what triggered rare instances of encephalomyelitis to smallpox vaccines. The animal model known as EAE continues to display its remarkable utility. Recent research, since the 70th-anniversary tribute, helps explain how Epstein-Barr virus triggers multiple sclerosis via molecular mimicry to a protein known as GlialCAM. Proteins with multiple domains similar to GlialCAM, tenascin, neuregulin, contactin, and protease kinase C inhibitors are present in the poxvirus family. These observations take us a full circle back to Rivers' first paper on EAE, 90 yr ago. The animal model for experimental encephalomyelitis, first published 90 yr ago, continues to illuminate mechanisms of disease. The model, initially developed to understand how smallpox triggers neuroinflammation on rare occasions, now moves full circle to its origins.