PATHOGENESIS OF VIRAL INDUCED DEMYELINATION

  • Rodriguez, Moses, (PI)

Project: Research project

Description

Mechanisms of demyelination are studied in two virus induced demyelinating
diseases in mice by means of electron microscopy, ultrastructural
immunolabeling techniques, and assays of cellular and humoral immunity
which use infected glial cells in tissue culture as targets. The
experimental models are induced by Theiler's murine encephalomyelitis virus
(TMEV) or the temperature sensitive mutant 472 of the Chandipura virus
(CV). The objectives in studying TMEV are 1) to determine definitively
wheter TMEV demyelination is immune mediated by transferring spleen cells
from mice during the development of the white matter lesion and searching
for histologic lesions in recipient mice, using as positive controls the
transfer of lymphoid cells from mice afflicted with experimental autoimmune
encephalomyelitis, 2) to determine if demyelination is the result of an
autoimmune process directed against myelin by desensitizing mice with
myelin components prior to infection with TMEV, 3) to determine if
demyelination is caused by neutral proteases released by macrophages by
attempting to prevent demyelination with neutral protease inhibitors and
macrophage depletion, 4) to determine if demyelination is caused by an
immune response directed against persistently infected oligodendroglial
cells by using persistently infected primary glial cultures as targets to
study lymphocytotoxicity. The objectives in studying the demyelination
associated with infective Chandipura virus are to determine 1) the
ultrastructural morphologic features of demyelination, 2) the
ultrastructural characteristics of the cells infected during various stages
of infection, 3) ultrastructural evidence of viral antigens expressed on
the surface of infected cells by using monospecific antibodies to the
structural proteins of TS472CV as probes to label antigens. The findings
are expected to contribute to the understanding of human demyelinating
diseases, such as multiple sclerosis.
StatusFinished
Effective start/end date12/1/8311/30/88

Funding

  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health

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Demyelinating Diseases
Theilovirus
Vesiculovirus
Neuroglia
Viral Antigens
Myelin Sheath
Infection
Protease Inhibitors
Multiple Sclerosis
Electron Microscopy
Peptide Hydrolases
Spleen
Macrophages
Lymphocytes
Viruses
Antigens
Temperature
Antibodies
Proteins

ASJC

  • Medicine(all)
  • Neuroscience(all)