Our goal here is to understand how several candidate viral infections enhance autoimmune disease in multiple sclerosis (EAE) and diabetes disease models (von Herrath and Fujinami). The novel aspects addressed by this PPG are: 1. The hypothesis that viral infections will be able to provide a 'fertile field' for autoaggressive lymphocytes or enhance already pre-existing but sub-clinical autoimmune processes. 2. The detailed mechanistic analysis involving mimicry as well as bystander activation, in particular the understanding of the basic mechanistic aspects of virally triggered presentation of autoantigens and activation of autoaggressive lymphocytes from the APC/immuno-proteasome side (Whitton). The emerging findings will be useful in pursuing the link between viruses and autoimmunity in humans in a more directional/mechanistic way.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Program Projects (P01)
Project #
5P01AI058105-04
Application #
7250836
Study Section
Special Emphasis Panel (ZAI1-NN-I (S1))
Program Officer
Esch, Thomas R
Project Start
2004-07-01
Project End
2009-06-30
Budget Start
2007-07-01
Budget End
2008-06-30
Support Year
4
Fiscal Year
2007
Total Cost
$1,112,562
Indirect Cost
Name
La Jolla Institute
Department
Type
DUNS #
603880287
City
La Jolla
State
CA
Country
United States
Zip Code
92037
Schneider, Darius A; von Herrath, Matthias G (2013) Viruses and Type 1 diabetes: a dynamic labile equilibrium. Diabetes Manag (Lond) 3:217-223
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Libbey, Jane E; Tsunoda, Ikuo; Fujinami, Robert S (2012) Possible role of interleukin-17 in a prime/challenge model of multiple sclerosis. J Neurovirol 18:471-8
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Fousteri, Georgia; Dave, Amy; Morin, Bret et al. (2011) Nasal cardiac myosin peptide treatment and OX40 blockade protect mice from acute and chronic virally-induced myocarditis. J Autoimmun 36:210-20
van Belle, Tom L; Coppieters, Ken T; von Herrath, Matthias G (2011) Type 1 diabetes: etiology, immunology, and therapeutic strategies. Physiol Rev 91:79-118
Bresson, Damien; Fousteri, Georgia; Manenkova, Yulia et al. (2011) Antigen-specific prevention of type 1 diabetes in NOD mice is ameliorated by OX40 agonist treatment. J Autoimmun 37:342-51
Van Belle, Tom L; Esplugues, Enric; Liao, Jeanette et al. (2011) Development of autoimmune diabetes in the absence of detectable IL-17A in a CD8-driven virally induced model. J Immunol 187:2915-22

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