Theiler's murine encephalomyelitis viruses (TMEV) strains can be divided into two subgroups on the basis of biological activities. The GDVII subgroup strains cause an acute, lethal neuronal disease with no virus persistence, while DA (TO) subgroup strains are less neurovirulent and produce a chronic demyelinating infection. Our major goal is to define viral genes and gene products critical for determining the virus' biological activities (neurovirulence, neurotropism, virus persistence). The TMEV system is a valuable one for such studies because of: the use of a mouse as an experimental host, the large amount of molecular information that will soon be available about this small virus with its small genome, the potential use of recombinant infectious cDNA from strains of both subgroups. We have a panel of TMEV neutralizing monoclonal antibodies (mAbs) and we are generating TMEV mutants resistant to them. We will sequence the epitopes of the neutralizing mAbs by RNA primer extension. The neutralization sites will be localized on the genome and virion structure. The importance of epitopes to TMEV's biological activities will be determined by observing the effect of inoculating mutants into mice. We have almost the whole of DA strain cloned and sequenced. We now plan to: clone and sequence FA strain (a member of the GDVII subgroup) and prepare DA and FA infectious cDNA. Recombinant infectious cDNA studies, guided by comparisons between sequences from both subgroups and by our mutant studies, will be performed to delineate parts of the genome critical for TMEV's biological activities. These studies may elucidate mechanisms of neuron tropism and injury relevant to motor neuron disease.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Specialized Center (P50)
Project #
5P50NS021442-06
Application #
3882321
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
6
Fiscal Year
1990
Total Cost
Indirect Cost
Name
University of Chicago
Department
Type
DUNS #
225410919
City
Chicago
State
IL
Country
United States
Zip Code
60637
Thomas, Ajit G; Bodner, Amos; Ghadge, Ghanashyam et al. (2009) GCP II inhibition rescues neurons from gp120IIIB-induced neurotoxicity. J Neurovirol 15:449-57
Haley, Benjamin; Paunesku, Tatjana; Proti?, Miroslava et al. (2009) Response of heterogeneous ribonuclear proteins (hnRNP) to ionising radiation and their involvement in DNA damage repair. Int J Radiat Biol 85:643-55
Paunesku, T; Chang-Liu, C M; Shearin-Jones, P et al. (2000) Identification of genes regulated by UV/salicylic acid. Int J Radiat Biol 76:189-98
Glaum, S R; Brooks, P A (1996) Tetanus-induced sustained potentiation of monosynaptic inhibitory transmission in the rat medulla: evidence for a presynaptic locus. J Neurophysiol 76:30-8
Brooks, P A; Glaum, S R (1995) GABAB receptors modulate a tetanus-induced sustained potentiation of monosynaptic inhibitory transmission in the rat nucleus tractus solitarii in vitro. J Auton Nerv Syst 54:16-26
Glaum, S R; Miller, R J (1995) Presynaptic metabotropic glutamate receptors modulate omega-conotoxin-GVIA-insensitive calcium channels in the rat medulla. Neuropharmacology 34:953-64
Siddique, T (1991) Molecular genetics of familial amyotrophic lateral sclerosis. Adv Neurol 56:227-31