Lactate dehydrogenase-elevating virus (LDV), a togavirus, naturally produces benign persistent infections characterized by continuous virus production in mice. Although, most isolates of LDV cause no overt disease in the mice they infect, one isolate, LDV-C, efficiently induces two distinct host strain specific diseases, poliomyelitis in C58 and AKR mice and meningitis and white matter inflammation in C57BR/cd mice. The LDV system provides a unique model for the study of genetically restricted host-virus interactions which lead to CNS neuropathology. The viral envelope (E) glycoprotein appears to be the key to understanding these complex host-virus interactions, since this protein should contain both the binding site for attachment to host cells and the immunodominant epitopes which elicit the host immune response. This proposal describes a study to characterize the LDV-E protein and to define its role in the induction of two different types of neuropathology. The E protein will be chemically characterized using glycosidase treatment and by amino acid and nucleic acid sequencing techniques. It will be analyzed antigenically using anti-E specific polyclonal and monoclonal antibodies. The in vitro B cell mitogenic activity of LDV and purified E protein will be evaluated. C58 mice appear to have LDV-specific receptors on their anterior motor neurons. We propose that while macrophages can be infected with either LDV or LDV-immune complexes, neurons can only be infected by LDV. To test this hypothesis, we will determine whether disease is more severe in B cell deficient c58 mice and conversely whether injection of anti-E antibody prior to infection reduces disease severity. Anti-E protein antibodies obtained during the proposed study may be useful for production of anti-idiotypic antibodies, which in turn could be used to localize and define virus- susceptible cell populations and virus receptors. Our preliminary data indicate that LDV-C infection of C57BR/cd mice may trigger an allergic encephalomyelitis response. We will attempt to induce this response in C57BR/cd mice in the absence of infection by immunization with purified E protein. The production of CNS tissue reactive autoantibodies by LDV-C infected mice will be investigated. The relative contribution of anti-E antibody or immune T cells to disease development will be investigated. Attempts will be made to infect cultured oligodendrocytes or astrocytes.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS019013-05
Application #
3399020
Study Section
Neurology C Study Section (NEUC)
Project Start
1983-12-01
Project End
1988-12-31
Budget Start
1988-09-01
Budget End
1988-12-31
Support Year
5
Fiscal Year
1988
Total Cost
Indirect Cost
Name
Wistar Institute
Department
Type
DUNS #
042250712
City
Philadelphia
State
PA
Country
United States
Zip Code
19104