C57B1/6 (B6) mice infected with mouse hepatitis virus, strain JHM (MHV) develop either an acute encephalitis or chronic demyelinating disease. This demyelinating disease is a model for the human disease multiple sclerosis. We are interested in the immunological mediators of demyelination in this model. In our model, a percentage of mice protected from the acute encephalitis by maternal antibody develop a demyelinating disease We have previously observed in this model of demyelination that roughly twenty percent of the lymphocytes infiltrating the CNS are B cells, although no serum antibody can be measured in these mice. Additionally, nude (athymic) mice develop a demyelinating disease in which some 70 percent of lymphocytes in the CNS are B cells. The function of these B cells has not been characterized. In order to investigate the role of these cells in demyelination, three specific aims will be pursued: 1) To characterize the nature of the B cell response in the MHV-infected CNS; 2) To investigate failure of antibody production in the chronic demyelinating disease; and 3) To determine the immunological effectors of MHV-JHM disease in nude mice.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Predoctoral Individual National Research Service Award (F31)
Project #
5F31NS042981-03
Application #
6779113
Study Section
Experimental Virology Study Section (EVR)
Program Officer
Nunn, Michael
Project Start
2001-12-19
Project End
2005-12-18
Budget Start
2003-12-19
Budget End
2004-12-18
Support Year
3
Fiscal Year
2004
Total Cost
$27,422
Indirect Cost
Name
University of Iowa
Department
Microbiology/Immun/Virology
Type
Schools of Medicine
DUNS #
062761671
City
Iowa City
State
IA
Country
United States
Zip Code
52242
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Dandekar, Ajai A; O'Malley, Katherine; Perlman, Stanley (2005) Important roles for gamma interferon and NKG2D in gammadelta T-cell-induced demyelination in T-cell receptor beta-deficient mice infected with a coronavirus. J Virol 79:9388-96
Dandekar, Ajai A; Anghelina, Daniela; Perlman, Stanley (2004) Bystander CD8 T-cell-mediated demyelination is interferon-gamma-dependent in a coronavirus model of multiple sclerosis. Am J Pathol 164:363-9
Dandekar, Ajai A; Jacobsen, Gary; Waldschmidt, Thomas J et al. (2003) Antibody-mediated protection against cytotoxic T-cell escape in coronavirus-induced demyelination. J Virol 77:11867-74
Dandekar, Ajai A; Perlman, Stanley (2002) Virus-induced demyelination in nude mice is mediated by gamma delta T cells. Am J Pathol 161:1255-63