Abstract

As in the previous year, the ongoing objective of this proposal is to utilize monoclonal antibodies to study the mechanism of JHM virus (JHMV) induced demyelination in experimental infections of mice. This animal model has many similarities to the human disease multiple sclerosis. During the next year, the following experiments will be performed. Further antigenic variant viruses will be generated. The variants will be used to map the structure of epitopes on the E2 protein of JHMV. The variants will also be use in detailed pathogenesis experiments. Double variants with two point mutations will also be generated and studied. The response of the immune system to the variants and the mechanisms underlying diminished neurovirulence will be explored. When the sequence of the gene for E2 becomes available, the location of variant mutations will be mapped. The tropism of variants in vitro organotypic cultures will be studied. Finally, attempts to produce antibody to the cellular receptor for JHMV will be undertaken, either by use of anti-idiotypic antibodies or immunization with receptor-positive cells. The use of rat-mouse monoclonal antibodies, as well as mouse-mouse monoclonal antibodies, will be explored when seeking anti-receptor antibodies.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Academic/Teacher Award (ATA) (K07)
Project #
5K07NS000795-04
Application #
3078154
Study Section
Neurological Disorders Program Project Review B Committee (NSPB)
Project Start
1983-07-01
Project End
1988-06-30
Budget Start
1986-07-01
Budget End
1987-06-30
Support Year
4
Fiscal Year
1986
Total Cost
Indirect Cost

  Institution

Name
University of Southern California
Department
Type
Schools of Medicine
DUNS #
041544081
City
Los Angeles
State
CA
Country
United States
Zip Code
90033

  Publications

Fleming, J O; Wang, F I; Trousdale, M D et al. (1993) Interaction of immune and central nervous systems: contribution of anti-viral Thy-1+ cells to demyelination induced by coronavirus JHM. Reg Immunol 5:37-43
Wang, F I; Hinton, D R; Gilmore, W et al. (1992) Sequential infection of glial cells by the murine hepatitis virus JHM strain (MHV-4) leads to a characteristic distribution of demyelination. Lab Invest 66:744-54
Matsushima, G K; Stohlman, S A (1991) Distinct subsets of accessory cells activate Thy-1+ triple negative (CD3-, CD4-, CD8-) cells and Th-1 delayed-type hypersensitivity effector T cells. J Immunol 146:3322-31
Wang, F I; Stohlman, S A; Fleming, J O (1990) Demyelination induced by murine hepatitis virus JHM strain (MHV-4) is immunologically mediated. J Neuroimmunol 30:31-41
Fleming, J O; Shubin, R A; Sussman, M A et al. (1989) Monoclonal antibodies to the matrix (E1) glycoprotein of mouse hepatitis virus protect mice from encephalitis. Virology 168:162-7
Fleming, J O; el Zaatari, F A; Gilmore, W et al. (1988) Antigenic assessment of coronaviruses isolated from patients with multiple sclerosis. Arch Neurol 45:629-33
Fleming, J O; Pen, L B (1988) Measurement of the concentration of murine IgG monoclonal antibody in hybridoma supernatants and ascites in absolute units by sensitive and reliable enzyme-linked immunosorbent assays (ELISA). J Immunol Methods 110:11-8
Fleming, J O; Trousdale, M D; Stohlman, S A et al. (1987) Pathogenic characteristics of neutralization-resistant variants of JHM coronavirus (MHV-4). Adv Exp Med Biol 218:333-42
Fleming, J O; Trousdale, M D; Bradbury, J et al. (1987) Experimental demyelination induced by coronavirus JHM (MHV-4): molecular identification of a viral determinant of paralytic disease. Microb Pathog 3:9-20
Fleming, J O; Keck, J G; Wei, T et al. (1987) Characterization of monoclonal antibodies to human OC43. Adv Exp Med Biol 218:517-20

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