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Multiple sclerosis: autoimmunity and viruses

Cusick, Matthew F.; Libbey, Jane E.; Fujinami, Robert S.

Current Opinion in Rheumatology: July 2013 - Volume 25 - Issue 4 - p 496–501
doi: 10.1097/BOR.0b013e328362004d
INFECTION AND AUTOIMMUNITY: Edited by Madeleine W. Cunningham

Purpose of review This review will explore two new aspects of the involvement of viruses in multiple sclerosis pathogenesis. The first aspect is the complex interactions between viruses. The second aspect is the proposal of a mechanism by which autoreactive T cells are able to escape thymic selection and potentially recognize self and a pathogen.

Recent findings With regard to viruses, recent work has demonstrated that one virus may enhance the replication of another virus, potentially leading to an increase in inflammation and disease progression. Also, interactions between human endogenous retroviruses, which likely do not replicate, and certain herpes viruses, may also play a role in disease pathogenesis. Mechanistically, T cells expressing dual T-cell receptors would be able to recognize self and a foreign antigen specifically. Therefore, human endogenous retroviruses potentially play a role in multiple sclerosis pathogenesis, and both interactions between multiple viruses and autoreactive CD8+ T cells with dual T-cell receptors may play a role in the pathogenesis of the disease.

Summary The complex interactions between multiple viral infections, either within the central nervous system or in the periphery, and the host immune response to viral infection may be such that a variety of viral specificities result in the activation of T cells that recognize self and induce multiple sclerosis. Therefore, it is unlikely that any one microbe will be determined to be the causative agent of multiple sclerosis as reflected by the number of potential triggering mechanisms of the disease.

Department of Pathology, University of Utah, Salt Lake City, Utah, USA

Correspondence to Robert S. Fujinami, PhD, Department of Pathology, University of Utah, 30 North 1900 East, 3R330 SOM, Salt Lake City, UT 84132, USA. Tel: +1 801 585 3305; fax: +1 801 585 3311; e-mail:

© 2013 Lippincott Williams & Wilkins, Inc.