title: Multiple sclerosis: autoimmunity and viruses.
abstract: OBJECTIVE
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors: Department of Pathology, University of Utah, Salt Lake City, Utah 84132, USA.
authors: Matthew F
authors: MF
authors: Cusick
authors: Jane E
authors: JE
authors: Libbey
authors: Robert S
authors: RS
authors: Fujinami
mesh_terms: D015551:Autoimmunity / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D006801:Humans; D008213:Lymphocyte Activation / Q000276:immunology; D009103:Multiple Sclerosis / Q000276:immunology* / Q000821:virology*; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D014777:Virus Diseases / Q000150:complications* / Q000276:immunology; D014779:Virus Replication
chemical_list: D011948:Receptors, Antigen, T-Cell
references: Biochim Biophys Acta. 2011 Feb;1812(2):151-61
references: 20637863
references: Biochim Biophys Acta. 2011 Feb;1812(2):132-40
references: 20600868
references: J Neuroimmunol. 2006 Mar;172(1-2):85-93
references: 16375978
references: J Immunol. 1976 Nov;117(5 Pt.2):1906-12
references: 993587
references: Autoimmune Dis. 2012;2012:969657
references: 22666554
references: Neuroscientist. 2011 Dec;17(6):659-76
references: 22130640
references: J Exp Med. 1995 Apr 1;181(4):1587-91
references: 7699339
references: J Neuroimmunol. 2012 Aug 15;249(1-2):105-8
references: 22608883
references: N Engl J Med. 2007 Aug 30;357(9):851-62
references: 17660530
references: Ann Neurol. 2001 Oct;50(4):434-42
references: 11601494
references: Mult Scler. 2004 Apr;10(2):145-8
references: 15124758
references: J Immunol. 2008 Nov 15;181(10):6934-41
references: 18981113
references: Science. 1993 Oct 15;262(5132):422-4
references: 8211163
references: J Immunol. 2012 Jan 1;188(1):477-86
references: 22116824
references: Retrovirology. 2009 Nov 16;6:104
references: 19917105
references: Nat Immunol. 2002 Feb;3(2):109-10
references: 11812982
references: Neurology. 2003 Apr 8;60(7):1157-62
references: 12682324
references: PLoS Pathog. 2011 Dec;7(12):e1002462
references: 22216008
references: Nat Immunol. 2010 Jul;11(7):628-34
references: 20526343
references: PLoS One. 2012;7(9):e44991
references: 23028727
references: J Neurol Sci. 1983 Dec;62(1-3):219-32
references: 6607973
references: Lancet Neurol. 2008 Sep;7(9):841-51
references: 18703006
references: Brain. 1999 Jan;122 ( Pt 1):17-26
references: 10050891
references: Biochim Biophys Acta. 2011 Feb;1812(2):162-76
references: 20696240
references: PLoS One. 2012;7(2):e32160
references: 22384166
references: Tissue Antigens. 1991 Jul;38(1):1-15
references: 1926129
references: J Exp Med. 1995 Oct 1;182(4):953-9
references: 7561698
references: J Neurovirol. 2012 Feb;18(1):45-54
references: 22281874
references: CNS Neurol Disord Drug Targets. 2012 Aug;11(5):528-44
references: 22583435
references: Proc Natl Acad Sci U S A. 1997 Jul 8;94(14):7583-8
references: 9207135
references: Lab Invest. 1982 Feb;46(2):171-85
references: 7062721
references: J Exp Med. 1993 Nov 1;178(5):1807-11
references: 8228827
references: Nat Med. 2008 Nov;14(11):1227-35
references: 18953350
references: Vaccine. 2011 Apr 12;29(17):3356-62
references: 20850537
references: J Neuropathol Exp Neurol. 2013 Jan;72(1):29-41
references: 23242282
references: Mult Scler. 2012 Dec;18(12):1721-36
references: 22457345
references: Ann Neurol. 2000 Dec;48(6):893-901
references: 11117546
references: Scand J Immunol. 1995 Dec;42(6):651-61
references: 8552989
references: Exp Neurol. 2010 Sep;225(1):2-8
references: 19840788
references: Nat Immunol. 2002 Feb;3(2):127-34
references: 11812989
references: PLoS One. 2011 Feb 02;6(2):e16652
references: 21311761
references: Int Immunol. 1999 Jan;11(1):113-9
references: 10050679
references: Mult Scler. 2004 Feb;10(1):26-34
references: 14760949
references: J Clin Invest. 2004 Mar;113(6):788-94
references: 15067307
references: Ann Neurol. 2006 Jul;60(1):12-21
references: 16802293
references: J Autoimmun. 2001 Jun;16(4):423-9
references: 11437490
references: J Immunol. 2008 Jul 1;181(1):136-45
references: 18566378
references: Nature. 2001 Feb 15;409(6822):860-921
references: 11237011
references: J Immunol. 2001 Dec 1;167(11):6158-64
references: 11714775
references: J Virol. 2012 Apr;86(7):3713-22
references: 22278236
references: Brain. 2007 Oct;130(Pt 10):2566-76
references: 17898009
references: N Engl J Med. 2000 Sep 28;343(13):938-52
references: 11006371
references: Tissue Antigens. 2000 Feb;55(2):140-8
references: 10746785
references: J Neuroimmunol. 1997 Mar;73(1-2):7-14
references: 9058754
references: J Immunol. 2004 Feb 1;172(3):1515-23
references: 14734729
references: J Virol. 1998 Apr;72(4):2671-6
references: 9525584
references: Acta Crystallogr D Biol Crystallogr. 2011 May;67(Pt 5):447-54
references: 21543847
references: Proc Natl Acad Sci U S A. 1994 Nov 8;91(23):10859-63
references: 7526383
references: Genome Res. 2011 Jul;21(7):1042-54
references: 21628452
references: J Exp Med. 1995 Apr 1;181(4):1391-8
references: 7699325
references: Brain. 2000 Jun;123 ( Pt 6):1174-83
references: 10825356
references: Results Probl Cell Differ. 2010;51:21-42
references: 19130026
references: J Virol. 2002 Dec;76(24):12834-44
references: 12438608
references: J Virol. 2000 Apr;74(7):3321-9
references: 10708449
references: J Exp Med. 2000 Aug 7;192(3):393-404
references: 10934227
references: Brain. 1997 Aug;120 ( Pt 8):1461-83
references: 9278635